Meme Kanseri Hücresinde Metilen Mavisi Aracili Fotodinamik Terapi ve Doksorubisinin Kombinasyonel Etkisi
Öz
Öz
Amaç: Meme kanseri kadınlarda görülen en sık kanser olup görülme sıklığı giderek artmaktadır. Günümüzde meme kanserinin tedavisinde cerrahi tedavi, radyasyon tedavisi ve kemoterapi gibi birçok yöntem vardır. Kemoterapi tedavisinde yaygın olarak kullanılan kemoterapötiklerden birisi olan doksorubisin (DOX) belirli bir dozun üzerinde tehlikeli yan etkilere ve ilaç direncine neden olur. Mevcut tedavilere kıyasla kombinasyon tedaviler son zamanlarda bu sorunların üstesinden gelmek için önem kazanmıştır. Bir fotoduyarlaştırıcı ile uygulanan fotodinamik terapi klinikte birçok kanser türünde uygulanmaktadır. Bu çalışma ile meme kanseri tedavisinde kullanılan DOX’u fotodinamik terapi (PDT) ile aktive edilen metilen mavisi (MB) ile kombinasyon uygulayarak DOX’un uygulanmasında düşük toksisite ile yüksek etkinlik alınması amaçlanmıştır.
Yöntem: MCF-7 meme kanseri hücre hattı üzerinde farklı konsantrasyonlarda DOX, MB, MB-PDT, DOX-PDT, MB-PDT+DOX ve DOX+MB-PDT olacak şekilde ayrı ayrı ve kombinasyon tedaviler denenmiştir. Hücre canlılığını belirlemek için MTT testi gerçekleştirilmiş ve hücrelerin %50 canlılık gösterdiği IC50 değerleri hesaplanmıştır. Ayrıca, MB ve DOX arasındaki etkileşimin derecesini belirlemek için kombinasyon indeksi (CI) değeri bulunmuştur. Ayrıca DOX ve fotodinamik terapi kombinasyonunun meme kanseri hücrelerine karşı apoptotik potansiyelini belirlemek için apoptotik ve antiapoptotik belirteçlerin (Bax, Bcl-2) mRNA ekspresyon seviyelerine RT-PCR ile bakılmıştır.
Bulgular: MB-PDT ve ardından düşük konsnatrasyonda DOX (428.4 nM ) kombinasyonunun, tek başına DOX'a ve önce DOX ardından MB-PDT’ye kıyasla kanser hücresi ölümünü indüklemede daha iyi bir etkiye sahip olduğunu göstermiştir. Aynı zamanda bu kombine uygulama Bcl-2 gen ekspresyonunu düşürürken, Bax gen ekspresyonunu yükselterek apoptotik potansiyelini göstermiştir.
Sonuç: Doksorubisin ve metilen mavisi ile indüklenmiş fotodinamik terapi kombine tedavisi meme kanseri hücreleri üzerinde sinerjik, sitotoksik ve apoptotik etkiler göstererek , umut verici bir yaklaşım sunmuştur.
Anahtar Kelimeler
Meme kanseri doksorubisin fotodinamik terapi metilen mavisi kombinasyon tedavi.
Etik Beyan
Bu çalışma etik kurul onayı gerektirmemektedir
Destekleyen Kurum
Yazarlar tarafından finansal destek almadıkları bildirilmiştir.
Kaynakça
- Sun YS, Zhao Z, Yang ZN, et al. Risk Factors and Preventions of Breast Cancer. Int J Biol Sci. 2017;13(11):1387-1397. doi:10.7150/ijbs.21635
- Jin X, Mu P. Targeting Breast Cancer Metastasis. Breast Cancer (Auckl). 2015;9(Suppl 1):23-34. doi:10.4137/BCBCR.S25460
- Ferrando-Díez A, Felip E, Pous A, Bergamino Sirven M, Margelí M. Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer. Cancers (Basel). 2022;14(14):3305. doi:10.3390/cancers14143305
- Elsawaf Z, Sinn HP. Triple-Negative Breast Cancer: Clinical and Histological Correlations. Breast Care (Basel). 2011;6(4):273-278. doi:10.1159/000331643
- Mangla B, Kohli K. Combination of Natural Agent with Synthetic Drug for the Breast Cancer Therapy. Int J Drug Dev & Res. 2018; 10: 22–26.
- Correia JH, Rodrigues JA, Pimenta S, Dong T, Yang Z. Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions. Pharmaceutics. 2021;13(9):1332. doi:10.3390/pharmaceutics13091332
- Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011;61(4):250-281. doi:10.3322/caac.20114
- Chen CW, Chan YC, Hsiao M, Liu RS. Plasmon-Enhanced Photodynamic Cancer Therapy by Upconversion Nanoparticles Conjugated with Au Nanorods. ACS Appl Mater Interfaces. 2016;8(47):32108-32119. doi:10.1021/acsami.6b07770
- Tardivo JP, Del Giglio A, de Oliveira CS, et al. Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications. Photodiagnosis Photodyn Ther. 2005;2(3):175-191. doi:10.1016/S1572-1000(05)00097-9
- Carvalho C, Santos RX, Cardoso S, et al. Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009;16(25):3267-3285. doi:10.2174/092986709788803312
- Meredith AM, Dass CR. Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism. J Pharm Pharmacol. 2016;68(6):729-741. doi:10.1111/jphp.12539
- Khodapasand E, Jafarzadeh N, et al. Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer? Iran Biomed J. 2015; 19(2): 69–75. 10.6091/ibj.1366.2015
- Sharifi S, Barar J, et al. Doxorubicin Changes Bax /Bcl-xL Ratio, Caspase-8 and 9 in Breast Cancer Cells. Adv Pharm Bull. 2015 Sep; 5(3): 351–359. https://doi.org/10.15171%2Fapb.2015.049
- Fisusi FA, Akala EO. Drug Combinations in Breast Cancer Therapy. Pharm Nanotechnol. 2019;7(1):3-23. doi:10.2174/2211738507666190122111224
- Palmer AC, Sorger PK. Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy. Cell. 2017;171(7):1678-1691.e13. doi:10.1016/j.cell.2017.11.009
- van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay. Methods Mol Biol. 2011;731:237-245. doi:10.1007/978-1-61779-080-5_20
- Palmer AC, Sorger PK. Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy. Cell. 2017;171(7):1678-1691.e13. doi:10.1016/j.cell.2017.11.009
- Hanušová V, Boušová I, Skálová L. Possibilities to increase the effectiveness of doxorubicin in cancer cells killing. Drug Metab Rev. 2011;43(4):540-557. doi:10.3109/03602532.2011.609174
- Usacheva MN, Teichert MC, Biel MA. The role of the methylene blue and toluidine blue monomers and dimers in the photoinactivation of bacteria. J Photochem Photobiol B. 2003;71(1-3):87-98. doi:10.1016/j.jphotobiol.2003.06.002
- Aniogo EC, George BPA, Abrahamse H. In vitro combined effect of Doxorubicin and sulfonated zinc Phthalocyanine-mediated photodynamic therapy on MCF-7 breast cancer cells. Tumour Biol. 2017;39(10):1010428317727278. doi:10.1177/1010428317727278
- Zakaria S, Gamal-Eldeen AM, El-Daly SM, Saleh S. Synergistic apoptotic effect of Doxil ® and aminolevulinic acid-based photodynamic therapy on human breast adenocarcinoma cells. Photodiagnosis Photodyn Ther. 2014;11(2):227-238. doi:10.1016/j.pdpdt.2014.03.001
- Dos Santos AF, Terra LF, Wailemann RA, et al. Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells. BMC Cancer. 2017;17(1):194. doi:10.1186/s12885-017-3179-7
- Yousefi Sadeghloo A, Khorsandi K, Kianmehr Z. Synergistic effect of photodynamic treatment and doxorubicin on triple negative breast cancer cells. Photochem Photobiol Sci. 2020;19(11):1580-1589. doi:10.1039/d0pp00132e
- Ferreto NP, Calaf GM. Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines. International Journal of Oncology. 2016; 3(6):753-762. doi.org/10.3892/ijo.2016.3558. 10.15171/apb.2015.049
Combinational Effect of Methylene Blue-Mediated Photodynamic Therapy and Doxorubicin on Breast Cancer Cells
Öz
Objective: Breast cancer is the most common cancer in women and its incidence is increasing. Today, there are many methods in the treatment of breast cancer, such as surgery, radiation therapy and chemotherapy. Doxorubicin (DOX), one of the chemotherapeutics commonly used in chemotherapy treatment, causes dangerous side effects and drug resistance above a certain dose. Thus, it reduces the effect of the treatment. Compared to existing treatments, combination therapies have recently gained importance to overcome these problems. Therefore, this study aimed to reduce the dose of DOX used in breast cancer treatment and increase the effectiveness of the treatment by combining it with methylene blue (MB) activated by photodynamic therapy (PDT).
Methods: Different concentrations of DOX, MB, MB-PDT, MB-PDT, DOX-PDT, MB-PDT+DOX and DOX+MB-PDT were tested separately and in combination on MCF-7 breast cancer cell line. MTT assay was performed to determine the cell viability and IC50 values were calculated where cells showed 50% viability. In addition, the combination index (CI) value was found to determine the degree of interaction between MB and DOX. In addition, mRNA expression levels of apoptotic and antiapoptotic markers (Bax, Bcl-2) were analysed by RT-PCR to determine the apoptotic potential of DOX and photodynamic therapy combination against breast cancer cells.
Results: The combination of MB-PDT followed by low concentrations of DOX (428.4 nM) had a better effect in inducing cancer cell death compared to DOX alone and DOX followed by MB-PDT. At the same time, this combined treatment showed its apoptotic potential by decreasing Bcl-2 gene expression and increasing Bax gene expression.
Conclusion: The combined treatment of doxorubicin and methylene blue-induced photodynamic therapy has shown synergistic, cytotoxic and apoptotic effects on breast cancer cells, offering a promising approach.
Anahtar Kelimeler
Breast cancer doxorubicin photodynamic therapy methylene blue combination therapy
Kaynakça
- Sun YS, Zhao Z, Yang ZN, et al. Risk Factors and Preventions of Breast Cancer. Int J Biol Sci. 2017;13(11):1387-1397. doi:10.7150/ijbs.21635
- Jin X, Mu P. Targeting Breast Cancer Metastasis. Breast Cancer (Auckl). 2015;9(Suppl 1):23-34. doi:10.4137/BCBCR.S25460
- Ferrando-Díez A, Felip E, Pous A, Bergamino Sirven M, Margelí M. Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer. Cancers (Basel). 2022;14(14):3305. doi:10.3390/cancers14143305
- Elsawaf Z, Sinn HP. Triple-Negative Breast Cancer: Clinical and Histological Correlations. Breast Care (Basel). 2011;6(4):273-278. doi:10.1159/000331643
- Mangla B, Kohli K. Combination of Natural Agent with Synthetic Drug for the Breast Cancer Therapy. Int J Drug Dev & Res. 2018; 10: 22–26.
- Correia JH, Rodrigues JA, Pimenta S, Dong T, Yang Z. Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions. Pharmaceutics. 2021;13(9):1332. doi:10.3390/pharmaceutics13091332
- Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011;61(4):250-281. doi:10.3322/caac.20114
- Chen CW, Chan YC, Hsiao M, Liu RS. Plasmon-Enhanced Photodynamic Cancer Therapy by Upconversion Nanoparticles Conjugated with Au Nanorods. ACS Appl Mater Interfaces. 2016;8(47):32108-32119. doi:10.1021/acsami.6b07770
- Tardivo JP, Del Giglio A, de Oliveira CS, et al. Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications. Photodiagnosis Photodyn Ther. 2005;2(3):175-191. doi:10.1016/S1572-1000(05)00097-9
- Carvalho C, Santos RX, Cardoso S, et al. Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009;16(25):3267-3285. doi:10.2174/092986709788803312
- Meredith AM, Dass CR. Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism. J Pharm Pharmacol. 2016;68(6):729-741. doi:10.1111/jphp.12539
- Khodapasand E, Jafarzadeh N, et al. Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer? Iran Biomed J. 2015; 19(2): 69–75. 10.6091/ibj.1366.2015
- Sharifi S, Barar J, et al. Doxorubicin Changes Bax /Bcl-xL Ratio, Caspase-8 and 9 in Breast Cancer Cells. Adv Pharm Bull. 2015 Sep; 5(3): 351–359. https://doi.org/10.15171%2Fapb.2015.049
- Fisusi FA, Akala EO. Drug Combinations in Breast Cancer Therapy. Pharm Nanotechnol. 2019;7(1):3-23. doi:10.2174/2211738507666190122111224
- Palmer AC, Sorger PK. Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy. Cell. 2017;171(7):1678-1691.e13. doi:10.1016/j.cell.2017.11.009
- van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay. Methods Mol Biol. 2011;731:237-245. doi:10.1007/978-1-61779-080-5_20
- Palmer AC, Sorger PK. Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy. Cell. 2017;171(7):1678-1691.e13. doi:10.1016/j.cell.2017.11.009
- Hanušová V, Boušová I, Skálová L. Possibilities to increase the effectiveness of doxorubicin in cancer cells killing. Drug Metab Rev. 2011;43(4):540-557. doi:10.3109/03602532.2011.609174
- Usacheva MN, Teichert MC, Biel MA. The role of the methylene blue and toluidine blue monomers and dimers in the photoinactivation of bacteria. J Photochem Photobiol B. 2003;71(1-3):87-98. doi:10.1016/j.jphotobiol.2003.06.002
- Aniogo EC, George BPA, Abrahamse H. In vitro combined effect of Doxorubicin and sulfonated zinc Phthalocyanine-mediated photodynamic therapy on MCF-7 breast cancer cells. Tumour Biol. 2017;39(10):1010428317727278. doi:10.1177/1010428317727278
- Zakaria S, Gamal-Eldeen AM, El-Daly SM, Saleh S. Synergistic apoptotic effect of Doxil ® and aminolevulinic acid-based photodynamic therapy on human breast adenocarcinoma cells. Photodiagnosis Photodyn Ther. 2014;11(2):227-238. doi:10.1016/j.pdpdt.2014.03.001
- Dos Santos AF, Terra LF, Wailemann RA, et al. Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells. BMC Cancer. 2017;17(1):194. doi:10.1186/s12885-017-3179-7
- Yousefi Sadeghloo A, Khorsandi K, Kianmehr Z. Synergistic effect of photodynamic treatment and doxorubicin on triple negative breast cancer cells. Photochem Photobiol Sci. 2020;19(11):1580-1589. doi:10.1039/d0pp00132e
- Ferreto NP, Calaf GM. Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines. International Journal of Oncology. 2016; 3(6):753-762. doi.org/10.3892/ijo.2016.3558. 10.15171/apb.2015.049
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Hücre Gelişimi, Proliferasyon ve Ölümü |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Haziran 2025 |
| Gönderilme Tarihi | 22 Haziran 2024 |
| Kabul Tarihi | 30 Mayıs 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 8 Sayı: 2 |
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