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Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor

Yıl 2023, Cilt: 27 Sayı: 2, 948 - 956, 27.06.2025

Saba Nikanfar Somayeh Atari-hajipirloo Fatemeh Kheradmand Amir Heydari

Öz

Combining agents with molecular targets can reduce monotherapy’s required dose and toxicity in cancer
treatment. In this study, we investigated the cellular viability and the mRNA expression of vascular endothelial growth
factor (VEGF) and nuclear factor kappa B (NF-κB) for the synergistic effects of imatinib and 2, 5- dimethylcelecoxib
(DMC) combination in human colorectal cancer cells. The effects of imatinib and DMC on cell viability were assessed by
MTT assay in HT-29 cells. The dose-effect relationships and drug interaction analyses were performed using the
CompuSyn Software. NF-κB and VEGF mRNA expression after treating cells with imatinib (7 µM) and DMC (24 µM)
separately and in combination (3.5 µM imatinib plus 12 µM DMC) were investigated using real-time RT-PCR. A strong
synergy was observed in most of the combined dose pairs of imatinib- DMC in the growth inhibition of HT-29 cancer
cells. Combined treatment with 3.5 µM imatinib and 12 µM DMC resulted in a significant (p ˂ 0.05) decrease in VEGF
and NF-κB mRNA levels as compared to the vehicle-treated control group. In addition, VEGF mRNA reduction was
significant at the mentioned concentrations for the imatinib-DMC combination compared to imatinib alone (p ˂ 0.05).
Our results suggest VEGF as one of the cyclooxygenase2 (COX-2) independent mechanisms for the synergistic effects of
imatinib-DMC. It would be beneficial to further evaluate the potential utilization of DMC for the anti-cancer application
while minimizing undesired side effects related to COX-2 inhibition and reducing the side effects of imatinib therapy.

Anahtar Kelimeler

Colorectal cancer Cyclooxygenase 2 2 5-dimethylcelecoxib NF-kappa B

Kaynakça

  • Pratschke KM, Atherton MJ, Sillito JA, Lamm CG. Evaluation of a modified proportional margins approach for surgical resection of mast cell tumors in dogs: 40 cases (2008–2012). J Am Vet Med Assoc. 2013; 243(10): 1436–1441. [CrossRef]
  • Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW. Colorectal cancer. Lancet. 2005; 365(9454): 153–165. [CrossRef]
  • Kumari S, Sherriff JM, Spooner D, Beckett R. Peripheral neuropathy induced by red yeast rice in a patient with a known small bowel gastrointestinal tumour. BMJ Case Rep. 2013; 2013:bcr2013009060. [CrossRef]
  • Attoub S, Rivat C, Rodrigues S, Van Bocxlaer S, Bedin M, Bruyneel E, et al. The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy. Cancer Res. 2002; 62: 4879–4883.
  • Stahtea XN, Roussidis AE, Kanakis I, Tzanakakis GN, Chalkiadakis G, Mavroudis D, Kletsas D, Karamanos NK. Imatinib inhibits colorectal cancer cell growth and suppresses stromal-induced growth stimulation, MT1-MMP expression and pro-MMP2 activation. Int J Cancer. 2007; 121(12): 2808–2814. [CrossRef]
  • Farag S, Verschoor AJ, Bosma JW, Gelderblom H, Kerst JM, Sleijfer S, Steeghs N. J Clin Pharmacol. 2015; 55:920– 925. [CrossRef]
  • Rossi F, Yozgat Y, de Stanchina E, Veach D, Clarkson B, Manova K, Giancotti FG, Antonescu CR, Besmer P. Imatinib upregulates compensatory integrin signaling in a mouse model of gastrointestinal stromal tumor and is more effective when combined with dasatinib. Mol Cancer Res. 2010; 8(9): 1271–1283. [CrossRef]
  • Hamoya T, Fujii G, Miyamoto S, Takahashi M, Totsuka Y, Wakabayashi K, Toshima J, Mutoh M. Effects of NSAIDs on the risk factors of colorectal cancer: a mini review. Genes Environ. 2016; 38(1): 1-7. [CrossRef]
  • Grancher A, Michel P, Di Fiore F, Sefrioui D. Aspirin and colorectal cancer. Bull Cancer. 2017; 105(2): 171-80. [CrossRef]
  • Schönthal AH. Anti-tumor properties of dimethyl-celecoxib, a derivative of celecoxib that does not inhibit cyclooxygenase-2: implications for glioma therapy. Neurosurg Focus. 2006; 20(4): E21. [CrossRef]
  • Backhus LM, Petasis NA, Uddin J, Schönthal AH, Bart RD, Lin Y, Starnes VA, Bremner RM. Dimethyl celecoxib as a novel non-cyclooxygenase 2 therapy in the treatment of non-small cell lung cancer. J Thorac Cardiovasc Surg. 2005; 130(5): 1406–1412. [CrossRef]
  • Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. Bmj. 2006; 332(7553): 1302-8. [CrossRef]
  • Garg A, Aggarwal BB. Nuclear transcription factor- kappaB as a target for cancer drug development. Leukemia. 2002; 16(6): 1053–1068. [CrossRef]
  • Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev. 2010; 21(1): 11–19. [CrossRef]
  • Carmeliet P. Blood vessels and nerves: Common signals, pathways and diseases. Vol. 4, Nature Reviews Genetics. 2003; 4(9): 710–720. [CrossRef]
  • Atari-Hajipirloo S, Nikanfar S, Heydari A, Kheradmand F. Imatinib and its combination with 2,5-dimethyl- celecoxibinduces apoptosis of human HT-29 colorectal cancer cells. Res Pharm Sci. 2017; 12(1): 67–73. [CrossRef]
  • Kelley RK, Hwang J, Magbanua MJM, Watt L, Beumer JH, Christner SM, Baruchel S, Wu B, Fong L, Yeh BM, Moore AP, Ko AH, Korn WM, Rajpal S, Park JW, Tempero MA, Venook AP, Bergsland EK. A phase 1 trial of imatinib, bevacizumab, and metronomic cyclophosphamide in advanced colorectal cancer. Br J Cancer. 2013; 109(7): 1725– 1734. [CrossRef]
  • Hoehler T, Von Wichert G, Schimanski C, Kanzler S, Moehler MH, Hinke A, Seufferlein T, Siebler J, Hochhaus A, Arnold D, Hallek M, Hofheinz R, Hacker UT. Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205. Br J Cancer. 2013; 109(6): 1408–1413. [CrossRef]
  • Abdel-Aziz AK, Azab SSE, Youssef SS, El-Sayed AM, El-Demerdash E, Shouman S. Modulation of imatinib cytotoxicity by selenite in HCT116 colorectal cancer cells. Basic Clin Pharmacol Toxicol. 2015; 116(1): 37–46. [CrossRef]
  • Radujkovic A, Topaly J, Fruehauf S, Zeller WJ. Combination treatment of imatinib-sensitive and -resistant BCR- ABL-positive CML cells with imatinib and farnesyltransferase inhibitors. Anticancer Res. 2006; 26(3 A): 2169–2177.
  • Dharmapuri G, Doneti R, Philip GH, Kalle AM. Celecoxib sensitizes imatinib-resistant K562 cells to imatinib by inhibiting MRP1-5, ABCA2 and ABCG2 transporters via Wnt and Ras signaling pathways. Leuk Res. 2015; 39(7): 696–701. [CrossRef]
  • Xiao H, Zhang Q, Lin Y, Reddy BS, Yang CS. Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int J Cancer. 2008; 122(9): 2115–2124. [CrossRef]
  • El-Awady RA, Saleh EM, Ezz M, Elsayed AM. Interaction of celecoxib with different anti-cancer drugs is antagonistic in breast but not in other cancer cells. Toxicol Appl Pharmacol. 2011; 255(3): 271–86. [CrossRef]
  • Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET. Celecoxib for the Prevention of Sporadic Colorectal Adenomas. N Engl J Med. 2006; 355(9): 873–884. [CrossRef]
  • Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B. Celecoxib for the Prevention of Colorectal Adenomatous Polyps. N Engl J Med. 2006; 355(9): 885–895. [CrossRef]
  • Atari-Hajipirloo S, Nikanfar S, Heydari A, Noori F, Kheradmand F. The effect of celecoxib and its combination with imatinib on human HT-29 colorectal cancer cells: Involvement of COX-2, Caspase-3, VEGF and NF-κB genes expression. Cell Mol Biol. 2016; 62(2): 68–74.
  • Li RJ, F.J.Gong GSZ. Cytotoxic activities of Celecoxib on leukemic cells and the synergistic effects of Celecoxib with Imatinib thereupon. Zhonghua Yi Xue Za Zhi. 2006; 86: 1417–1420
  • Arunasree KM, Roy KR, Anilkumar K, Aparna A, Reddy GV, Reddanna P. Imatinib-resistant K562 cells are more sensitive to celecoxib, a selective COX-2 inhibitor: Role of COX-2 and MDR-1. Leuk Res. 2008; 32(6): 855–864. [CrossRef]
  • Schultz JD, Rotunno S, Riedel F, Anders C, Erben P, Hofheinz RD, Faber A, Thorn C, Sommer JU, Hörmann K, Sauter A. Synergistic effects of imatinib and carboplatin on VEGF, PDGF and PDGF-Rα/β expression in squamous cell carcinoma of the head and neck in vitro. Int J Oncol. 2011; 38(4): 1001–1012. [CrossRef]
  • Virrey JJ, Liu Z, Cho H-Y, Kardosh A, Golden EB, Louie SG, Gaffney KJ, Petasis NA, Schönthal AH, Chen TC, Hofman FM. Antiangiogenic Activities of 2,5-Dimethyl-Celecoxib on the Tumor Vasculature. Mol Cancer Ther. 2010; 9(3): 631–641. [CrossRef]
  • osadas EM, Kwitkowski V, Kotz HL, Espina V, Minasian L, Tchabo N, Premkumar A, Hussain MM, Chang R, Steinberg SM, Kohn EC. A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling. Cancer. 2007; 110(2): 309–317. [CrossRef]
  • Xu B, Wang Y, Yang J, Zhang Z, Zhang Y, Du H. Celecoxib induces apoptosis but up-regulates VEGF via endoplasmic reticulum stress in human colorectal cancer in vitro and in vivo. Cancer Chemother Pharmacol. 2016; 77(4): 797–806. [CrossRef]
  • Kim DS, Na YJ, Kang MH, Yoon SY, Choi CW. Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells. Korean J Intern Med. 2016; 31(2): 357–366. [CrossRef]
  • Kardosh A, Soriano N, Liu YT, Uddin J, Petasis NA, Hofman FM, Chen TC, Schönthal AH. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood. 2005; 106(13): 4330–4338. [CrossRef]
  • Deckmann K, Rörsch F, Geisslinger G, Grösch S. Dimethylcelecoxib induces an inhibitory complex consisting of HDAC1/NF-κB(p65)RelA leading to transcriptional downregulation of mPGES-1 and EGR1. Cell Signal. 2012; 24(2): 460–467. [CrossRef]
  • Tseng PH, Lin HP, Zhu J, Chen KF, Hade EM, Young DC, Byrd JC, Grever M, Johnson K, Druker BJ, Chen CS. Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance. Blood. 2005; 105(10): 4021–4027. [CrossRef]
  • Yang Z, Xiao H, Jin H, Koo PT, Tsang DJ, Yang CS. Synergistic actions of atorvastatin with gamma-tocotrienol and celecoxib against human colon cancer HT29 and HCT116 cells. Int J Cancer. 2010; 126(4): 852-63. [CrossRef]
  • Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984; 22: 27–55. [CrossRef]
  • Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006; 58(3): 621-81. [CrossRef]
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(- Delta Delta C(T)) Method. Methods. 2001; 25(4): 402–408. [CrossRef]

Yıl 2023, Cilt: 27 Sayı: 2, 948 - 956, 27.06.2025

Saba Nikanfar Somayeh Atari-hajipirloo Fatemeh Kheradmand Amir Heydari

Öz

Kaynakça

  • Pratschke KM, Atherton MJ, Sillito JA, Lamm CG. Evaluation of a modified proportional margins approach for surgical resection of mast cell tumors in dogs: 40 cases (2008–2012). J Am Vet Med Assoc. 2013; 243(10): 1436–1441. [CrossRef]
  • Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW. Colorectal cancer. Lancet. 2005; 365(9454): 153–165. [CrossRef]
  • Kumari S, Sherriff JM, Spooner D, Beckett R. Peripheral neuropathy induced by red yeast rice in a patient with a known small bowel gastrointestinal tumour. BMJ Case Rep. 2013; 2013:bcr2013009060. [CrossRef]
  • Attoub S, Rivat C, Rodrigues S, Van Bocxlaer S, Bedin M, Bruyneel E, et al. The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy. Cancer Res. 2002; 62: 4879–4883.
  • Stahtea XN, Roussidis AE, Kanakis I, Tzanakakis GN, Chalkiadakis G, Mavroudis D, Kletsas D, Karamanos NK. Imatinib inhibits colorectal cancer cell growth and suppresses stromal-induced growth stimulation, MT1-MMP expression and pro-MMP2 activation. Int J Cancer. 2007; 121(12): 2808–2814. [CrossRef]
  • Farag S, Verschoor AJ, Bosma JW, Gelderblom H, Kerst JM, Sleijfer S, Steeghs N. J Clin Pharmacol. 2015; 55:920– 925. [CrossRef]
  • Rossi F, Yozgat Y, de Stanchina E, Veach D, Clarkson B, Manova K, Giancotti FG, Antonescu CR, Besmer P. Imatinib upregulates compensatory integrin signaling in a mouse model of gastrointestinal stromal tumor and is more effective when combined with dasatinib. Mol Cancer Res. 2010; 8(9): 1271–1283. [CrossRef]
  • Hamoya T, Fujii G, Miyamoto S, Takahashi M, Totsuka Y, Wakabayashi K, Toshima J, Mutoh M. Effects of NSAIDs on the risk factors of colorectal cancer: a mini review. Genes Environ. 2016; 38(1): 1-7. [CrossRef]
  • Grancher A, Michel P, Di Fiore F, Sefrioui D. Aspirin and colorectal cancer. Bull Cancer. 2017; 105(2): 171-80. [CrossRef]
  • Schönthal AH. Anti-tumor properties of dimethyl-celecoxib, a derivative of celecoxib that does not inhibit cyclooxygenase-2: implications for glioma therapy. Neurosurg Focus. 2006; 20(4): E21. [CrossRef]
  • Backhus LM, Petasis NA, Uddin J, Schönthal AH, Bart RD, Lin Y, Starnes VA, Bremner RM. Dimethyl celecoxib as a novel non-cyclooxygenase 2 therapy in the treatment of non-small cell lung cancer. J Thorac Cardiovasc Surg. 2005; 130(5): 1406–1412. [CrossRef]
  • Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. Bmj. 2006; 332(7553): 1302-8. [CrossRef]
  • Garg A, Aggarwal BB. Nuclear transcription factor- kappaB as a target for cancer drug development. Leukemia. 2002; 16(6): 1053–1068. [CrossRef]
  • Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev. 2010; 21(1): 11–19. [CrossRef]
  • Carmeliet P. Blood vessels and nerves: Common signals, pathways and diseases. Vol. 4, Nature Reviews Genetics. 2003; 4(9): 710–720. [CrossRef]
  • Atari-Hajipirloo S, Nikanfar S, Heydari A, Kheradmand F. Imatinib and its combination with 2,5-dimethyl- celecoxibinduces apoptosis of human HT-29 colorectal cancer cells. Res Pharm Sci. 2017; 12(1): 67–73. [CrossRef]
  • Kelley RK, Hwang J, Magbanua MJM, Watt L, Beumer JH, Christner SM, Baruchel S, Wu B, Fong L, Yeh BM, Moore AP, Ko AH, Korn WM, Rajpal S, Park JW, Tempero MA, Venook AP, Bergsland EK. A phase 1 trial of imatinib, bevacizumab, and metronomic cyclophosphamide in advanced colorectal cancer. Br J Cancer. 2013; 109(7): 1725– 1734. [CrossRef]
  • Hoehler T, Von Wichert G, Schimanski C, Kanzler S, Moehler MH, Hinke A, Seufferlein T, Siebler J, Hochhaus A, Arnold D, Hallek M, Hofheinz R, Hacker UT. Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205. Br J Cancer. 2013; 109(6): 1408–1413. [CrossRef]
  • Abdel-Aziz AK, Azab SSE, Youssef SS, El-Sayed AM, El-Demerdash E, Shouman S. Modulation of imatinib cytotoxicity by selenite in HCT116 colorectal cancer cells. Basic Clin Pharmacol Toxicol. 2015; 116(1): 37–46. [CrossRef]
  • Radujkovic A, Topaly J, Fruehauf S, Zeller WJ. Combination treatment of imatinib-sensitive and -resistant BCR- ABL-positive CML cells with imatinib and farnesyltransferase inhibitors. Anticancer Res. 2006; 26(3 A): 2169–2177.
  • Dharmapuri G, Doneti R, Philip GH, Kalle AM. Celecoxib sensitizes imatinib-resistant K562 cells to imatinib by inhibiting MRP1-5, ABCA2 and ABCG2 transporters via Wnt and Ras signaling pathways. Leuk Res. 2015; 39(7): 696–701. [CrossRef]
  • Xiao H, Zhang Q, Lin Y, Reddy BS, Yang CS. Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int J Cancer. 2008; 122(9): 2115–2124. [CrossRef]
  • El-Awady RA, Saleh EM, Ezz M, Elsayed AM. Interaction of celecoxib with different anti-cancer drugs is antagonistic in breast but not in other cancer cells. Toxicol Appl Pharmacol. 2011; 255(3): 271–86. [CrossRef]
  • Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET. Celecoxib for the Prevention of Sporadic Colorectal Adenomas. N Engl J Med. 2006; 355(9): 873–884. [CrossRef]
  • Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B. Celecoxib for the Prevention of Colorectal Adenomatous Polyps. N Engl J Med. 2006; 355(9): 885–895. [CrossRef]
  • Atari-Hajipirloo S, Nikanfar S, Heydari A, Noori F, Kheradmand F. The effect of celecoxib and its combination with imatinib on human HT-29 colorectal cancer cells: Involvement of COX-2, Caspase-3, VEGF and NF-κB genes expression. Cell Mol Biol. 2016; 62(2): 68–74.
  • Li RJ, F.J.Gong GSZ. Cytotoxic activities of Celecoxib on leukemic cells and the synergistic effects of Celecoxib with Imatinib thereupon. Zhonghua Yi Xue Za Zhi. 2006; 86: 1417–1420
  • Arunasree KM, Roy KR, Anilkumar K, Aparna A, Reddy GV, Reddanna P. Imatinib-resistant K562 cells are more sensitive to celecoxib, a selective COX-2 inhibitor: Role of COX-2 and MDR-1. Leuk Res. 2008; 32(6): 855–864. [CrossRef]
  • Schultz JD, Rotunno S, Riedel F, Anders C, Erben P, Hofheinz RD, Faber A, Thorn C, Sommer JU, Hörmann K, Sauter A. Synergistic effects of imatinib and carboplatin on VEGF, PDGF and PDGF-Rα/β expression in squamous cell carcinoma of the head and neck in vitro. Int J Oncol. 2011; 38(4): 1001–1012. [CrossRef]
  • Virrey JJ, Liu Z, Cho H-Y, Kardosh A, Golden EB, Louie SG, Gaffney KJ, Petasis NA, Schönthal AH, Chen TC, Hofman FM. Antiangiogenic Activities of 2,5-Dimethyl-Celecoxib on the Tumor Vasculature. Mol Cancer Ther. 2010; 9(3): 631–641. [CrossRef]
  • osadas EM, Kwitkowski V, Kotz HL, Espina V, Minasian L, Tchabo N, Premkumar A, Hussain MM, Chang R, Steinberg SM, Kohn EC. A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling. Cancer. 2007; 110(2): 309–317. [CrossRef]
  • Xu B, Wang Y, Yang J, Zhang Z, Zhang Y, Du H. Celecoxib induces apoptosis but up-regulates VEGF via endoplasmic reticulum stress in human colorectal cancer in vitro and in vivo. Cancer Chemother Pharmacol. 2016; 77(4): 797–806. [CrossRef]
  • Kim DS, Na YJ, Kang MH, Yoon SY, Choi CW. Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells. Korean J Intern Med. 2016; 31(2): 357–366. [CrossRef]
  • Kardosh A, Soriano N, Liu YT, Uddin J, Petasis NA, Hofman FM, Chen TC, Schönthal AH. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood. 2005; 106(13): 4330–4338. [CrossRef]
  • Deckmann K, Rörsch F, Geisslinger G, Grösch S. Dimethylcelecoxib induces an inhibitory complex consisting of HDAC1/NF-κB(p65)RelA leading to transcriptional downregulation of mPGES-1 and EGR1. Cell Signal. 2012; 24(2): 460–467. [CrossRef]
  • Tseng PH, Lin HP, Zhu J, Chen KF, Hade EM, Young DC, Byrd JC, Grever M, Johnson K, Druker BJ, Chen CS. Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance. Blood. 2005; 105(10): 4021–4027. [CrossRef]
  • Yang Z, Xiao H, Jin H, Koo PT, Tsang DJ, Yang CS. Synergistic actions of atorvastatin with gamma-tocotrienol and celecoxib against human colon cancer HT29 and HCT116 cells. Int J Cancer. 2010; 126(4): 852-63. [CrossRef]
  • Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984; 22: 27–55. [CrossRef]
  • Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006; 58(3): 621-81. [CrossRef]
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(- Delta Delta C(T)) Method. Methods. 2001; 25(4): 402–408. [CrossRef]
Toplam 40 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık Biyokimyası
Bölüm Articles
Yazarlar

Saba Nikanfar 0000-0003-2824-1837

Somayeh Atari-hajipirloo 0000-0002-9812-3660

Fatemeh Kheradmand

Amir Heydari 0000-0003-3850-053X

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 2

Kaynak Göster

APA Nikanfar, S., Atari-hajipirloo, S., Kheradmand, F., Heydari, A. (2025). Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor. Journal of Research in Pharmacy, 27(2), 948-956.
AMA Nikanfar S, Atari-hajipirloo S, Kheradmand F, Heydari A. Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor. J. Res. Pharm. Haziran 2025;27(2):948-956.
Chicago Nikanfar, Saba, Somayeh Atari-hajipirloo, Fatemeh Kheradmand, ve Amir Heydari. “Imatinib Synergizes With 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor”. Journal of Research in Pharmacy 27, sy. 2 (Haziran 2025): 948-56.
EndNote Nikanfar S, Atari-hajipirloo S, Kheradmand F, Heydari A (01 Haziran 2025) Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor. Journal of Research in Pharmacy 27 2 948–956.
IEEE S. Nikanfar, S. Atari-hajipirloo, F. Kheradmand, ve A. Heydari, “Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor”, J. Res. Pharm., c. 27, sy. 2, ss. 948–956, 2025.
ISNAD Nikanfar, Saba vd. “Imatinib Synergizes With 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor”. Journal of Research in Pharmacy 27/2 (Haziran 2025), 948-956.
JAMA Nikanfar S, Atari-hajipirloo S, Kheradmand F, Heydari A. Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor. J. Res. Pharm. 2025;27:948–956.
MLA Nikanfar, Saba vd. “Imatinib Synergizes With 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor”. Journal of Research in Pharmacy, c. 27, sy. 2, 2025, ss. 948-56.
Vancouver Nikanfar S, Atari-hajipirloo S, Kheradmand F, Heydari A. Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor. J. Res. Pharm. 2025;27(2):948-56.