بررسی اثر داروهای اگزالی‌پلاتین و پاکلی تاکسل برسلول‌های سرطان کولون (HT29) و آنالیز بیان ژن‌های آپوپتوزی کاسپاز3، کاسپاز9 وP53
الموضوعات :
هما محمودزاده
1
,
جواد بهارآرا
2
,
یگانه رضایی دلویی
3
1 - گروه زیست شناسی-دانشگاه ازاد اسلامی- واحد مشهد
2 - گروه زیست شناسی-دانشگاه ازاد اسلامی- واحد مشهد
3 - گروه زیست شناسی دانشگاه آزاد اسلامی واحد مشهد، مشهد، ایران
تاريخ الإرسال : 28 الجمعة , محرم, 1444
تاريخ التأكيد : 01 الثلاثاء , شعبان, 1444
تاريخ الإصدار : 05 الأحد , محرم, 1445
الکلمات المفتاحية:
سرطان کولون,
ژن p53,
اگزالی‌پلاتین,
پاکلی‌تاکسل,
ژن کاسپاز,
ملخص المقالة :
هدف: هدف بررسی اثرات سمیت سلولی پاکلی‌تاکسل و اگزالی‌پلاتین بر رده سلولی سرطان کولون (HT29) و آنالیز بیان ژن‌های آپوپتوزی کاسپاز 3، 9و P53 می‌باشد. مواد و روش ها: ابتدا سمیت سلولی داروهای پاکلی‌تاکسل و اگزالی پلاتین و اثر توام آنها با غلظت‌های مختلف بر رده سلولی HT29 با روش MTT بررسی شد و غلظت 50 درصد کشندگی (IC50) آن تعیین شد. میزان بیان ژن‌های آپوپتوزی کاسپاز 3 و 9 نسبت به ژن مرجع GAPDH با استفاده از روش Real-Time PCR بررسی شد. هم چنین بررسی آپوپتوز سلول ها با استفاده از رنگ آمیزی Annexin V/PI و DAPI انجام شد. نتایج :پاکلی‌تاکسل و اگزالی‌پلاتین به ترتیب در غلظت های 25/3 و 00062/0 میکروگرم در میلیلیتر بیشترین اثر سمیت سلولی را دارد و میزان IC50 آن 00016/0 و µg/ml 5/12 محاسبه شد. تیمار همزمان داروها زنده‌مانی سلول‌ها را کاهش داد . بیان ژن‌های کاسپاز 3 و 9, P53 نسبت به ژن مرجع GAPDH در سلول های سرطان کولون تیمار شده نیز افزایش یافت. نتایج آزمون DAPI نشان دهنده ی قطعه قطعه شدن هسته‌ها و آپوپتوز در گروههای تیماری همزمان بود. بررسی آپوپتوز با استفاده از Annexin V/PI نشان می‌دهد که 98 درصد سلول‌های گروه شاهد سالم می باشند و درصد زیادی از سلول‌ها تحت تیمار دچار آپوپتوز شده اند . نتیجه گیری: با توجه به سمیت سلولی و القای فرایند آپوپتوزیس در رده سلولی سرطان کولون توسط داروهای پاکلی‌تاکسل و اگزالی-پلاتین، میتوان نتیجه‌گیری کرد که این داروها گزینه مناسب جهت درمان سرطان کولون می باشند.
المصادر:
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Levi M, Shalgi R, Brenner B, Perl G, Purim O, Amit L, Stemmer S M, Ben-Aharon I. The impact of oxaliplatin on the gonads: from bedside to the bench. Mol Hum Reprod, 2015; 21(12), 885-893. https://doi.org/10.1093/molehr/gav055
Feng L X, Li M, Liu Y J, Yang S M, Zhang N. Synergistic enhancement of cancer therapy using a combination of ceramide and docetaxel. Int J Mol Sci, 2014; 15(3), 4201-4220. https://doi.org/10.3390/ijms15034201
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Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol, 2019; 14(2), 89-103. https://doi.org/10.5114/pg.2018.81072
Mendiratta G, Ke E, Aziz M, Liarakos D, Tong M, Stites E C. Cancer gene mutation frequencies for the U.S. population. Nature Communications, 2021; 12(1), 5961. https://doi.org/10.1038/s41467-021-26213-y
Beijers A J, Mols F, Vreugdenhil G. A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration. Support Care Cancer, 2015; 22(7), 1999-2007. https://doi.org/10.1007/s00520-014-2242-z
Danciu C, Muntean D, Alexa E, Farcas C, Oprean C, Zupko I, Bor A, Minda D, Proks M, Buda V, Hancianu M, Cioanca O, Soica C, Popescu S, Dehelean C A. Phytochemical Characterization and Evaluation of the Antimicrobial, Antiproliferative and Pro-Apoptotic Potential of Ephedra alata Decne. Hydroalcoholic Extract against the MCF-7 Breast Cancer Cell Line. Molecules, 2018; 24(1). https://doi.org/10.3390/molecules24010013
Azman A S, Othman I, Fang C M, Chan K G, Goh B H, Lee L H. Antibacterial, Anticancer and Neuroprotective Activities of Rare Actinobacteria from Mangrove Forest Soils. Indian J Microbiol,2017; 57(2), 177-187. https://doi.org/10.1007/s12088-016-0627-z
Fujie Y, Yamamoto H, Ngan C Y, Takagi A, Hayashi T, Suzuki R, Ezumi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M. Oxaliplatin, a potent inhibitor of survivin, enhances paclitaxel-induced apoptosis and mitotic catastrophe in colon cancer cells. Jpn J Clin Oncol, 2005; 35(8), 453-463. https://doi.org/10.1093/jjco/hyi130
Hopkins B D, Goncalves M D, Cantley L C. Obesity and Cancer Mechanisms: Cancer Metabolism. J Clin Oncol, 2016; 34(35), 4277-4283. https://doi.org/10.1200/jco.2016.67.9712
Kratz F, Müller I A, Ryppa C, Warnecke A. Prodrug strategies in anticancer chemotherapy. ChemMedChem, 2008; 3(1), 20-53. https://doi.org/10.1002/cmdc.200700159
MacKenzie S H, Clark A C. Targeting cell death in tumors by activating caspases. Curr Cancer Drug Targets, 2008; 8(2), 98-109. https://doi.org/10.2174/156800908783769391
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4): 495-516
Ahmed AA, Wang X, Lu Z, et al. Modulating microtubule stability enhances the cytotoxic response of cancer cells to paclitaxel. Cancer Res. 2011; 71(17): 5806–5817.
Oechsle K, Kollmannsberger C, Honecker F, Mayer F. Long-term survival after treatment with gemcitabine and oxaliplatin with and without paclitaxel plus secondary surgery in patients with cisplatin-refractory and/or multiply relapsed germ cell tumors. Eur Urol, 2011; 60(4):850-5. doi: 10.1016/j.eururo.2011.06.019.
Zhang Y, Li C, Qin Small extracellular vesicles ameliorate peripheral neuropathy and enhance chemotherapy of oxaliplatin on ovarian cancer. J. E. V., (2021); 10 (5). https://doi.org/10.1002/jev2.12073
Shi M, Yang Z, Lu S. Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases. BMC Cancer, 2021; 21, 1344. https://doi.org/10.1186/s12885-021-09027-5
Berlin JD, Venook A, Bergsland E, Rothenberg M, Lockhart AC, Rosen L. Colorectal Cancer. 2008;7(1): 44-7. doi: 10.3816/CCC.2008.n.006.
Cook L M, Hurst D R, Welch D R. Metastasis suppressors and the tumor microenvironment. Semin Cancer Biol, 2011; 21(2), 113-122. https://doi.org/10.1016/j.semcancer.2010.12.005
Arnold J, David P. The P53 family: a subject collection from cold spring Harbor perspectives in biology laboratory press. Molecular cancer, 2010; 126:273-84.
Yonezawa A, Masuda S, Yokoo S, Katsura T, Inui K. Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family) J. Pharmacol. Exp. Ther. 2006; 19: 879–886. doi:10.1124/jpet.106.110346.
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Grimes M, Hall B, Foltz L, Levy T, Rikova K, Gaiser J, Cook W, Wheeler T., Clark N R, Lachmann A, Zhang B, Hornbeck P, Ma'ayan A, Comb M. Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks. 2018; Sci Signal, 11(531). https://doi.org/10.1126/scisignal.aaq1087
Haque I, Ghosh A, Acup S, Banerjee S, Dhar K, Ray A, Sarkar S, Kambhampati S, Banerjee S K. Leptin-induced ER-α-positive breast cancer cell viability and migration is mediated by suppressing CCN5-signaling via activating JAK/AKT/STAT-pathway. BMC Cancer, 2018; 18(1), 99. https://doi.org/10.1186/s12885-018-3993-6
Levi M, Shalgi R, Brenner B, Perl G, Purim O, Amit L, Stemmer S M, Ben-Aharon I. The impact of oxaliplatin on the gonads: from bedside to the bench. Mol Hum Reprod, 2015; 21(12), 885-893. https://doi.org/10.1093/molehr/gav055
Feng L X, Li M, Liu Y J, Yang S M, Zhang N. Synergistic enhancement of cancer therapy using a combination of ceramide and docetaxel. Int J Mol Sci, 2014; 15(3), 4201-4220. https://doi.org/10.3390/ijms15034201
Sung H, Ferlay J, Siegel R L, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 2021; 71(3), 209-249. https://doi.org/10.3322/caac.21660
Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol, 2019; 14(2), 89-103. https://doi.org/10.5114/pg.2018.81072
Mendiratta G, Ke E, Aziz M, Liarakos D, Tong M, Stites E C. Cancer gene mutation frequencies for the U.S. population. Nature Communications, 2021; 12(1), 5961. https://doi.org/10.1038/s41467-021-26213-y
Beijers A J, Mols F, Vreugdenhil G. A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration. Support Care Cancer, 2015; 22(7), 1999-2007. https://doi.org/10.1007/s00520-014-2242-z
Danciu C, Muntean D, Alexa E, Farcas C, Oprean C, Zupko I, Bor A, Minda D, Proks M, Buda V, Hancianu M, Cioanca O, Soica C, Popescu S, Dehelean C A. Phytochemical Characterization and Evaluation of the Antimicrobial, Antiproliferative and Pro-Apoptotic Potential of Ephedra alata Decne. Hydroalcoholic Extract against the MCF-7 Breast Cancer Cell Line. Molecules, 2018; 24(1). https://doi.org/10.3390/molecules24010013
Azman A S, Othman I, Fang C M, Chan K G, Goh B H, Lee L H. Antibacterial, Anticancer and Neuroprotective Activities of Rare Actinobacteria from Mangrove Forest Soils. Indian J Microbiol,2017; 57(2), 177-187. https://doi.org/10.1007/s12088-016-0627-z
Fujie Y, Yamamoto H, Ngan C Y, Takagi A, Hayashi T, Suzuki R, Ezumi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M. Oxaliplatin, a potent inhibitor of survivin, enhances paclitaxel-induced apoptosis and mitotic catastrophe in colon cancer cells. Jpn J Clin Oncol, 2005; 35(8), 453-463. https://doi.org/10.1093/jjco/hyi130
Hopkins B D, Goncalves M D, Cantley L C. Obesity and Cancer Mechanisms: Cancer Metabolism. J Clin Oncol, 2016; 34(35), 4277-4283. https://doi.org/10.1200/jco.2016.67.9712
Kratz F, Müller I A, Ryppa C, Warnecke A. Prodrug strategies in anticancer chemotherapy. ChemMedChem, 2008; 3(1), 20-53. https://doi.org/10.1002/cmdc.200700159
MacKenzie S H, Clark A C. Targeting cell death in tumors by activating caspases. Curr Cancer Drug Targets, 2008; 8(2), 98-109. https://doi.org/10.2174/156800908783769391
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4): 495-516
Ahmed AA, Wang X, Lu Z, et al. Modulating microtubule stability enhances the cytotoxic response of cancer cells to paclitaxel. Cancer Res. 2011; 71(17): 5806–5817.
Oechsle K, Kollmannsberger C, Honecker F, Mayer F. Long-term survival after treatment with gemcitabine and oxaliplatin with and without paclitaxel plus secondary surgery in patients with cisplatin-refractory and/or multiply relapsed germ cell tumors. Eur Urol, 2011; 60(4):850-5. doi: 10.1016/j.eururo.2011.06.019.
Zhang Y, Li C, Qin Small extracellular vesicles ameliorate peripheral neuropathy and enhance chemotherapy of oxaliplatin on ovarian cancer. J. E. V., (2021); 10 (5). https://doi.org/10.1002/jev2.12073
Shi M, Yang Z, Lu S. Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases. BMC Cancer, 2021; 21, 1344. https://doi.org/10.1186/s12885-021-09027-5
Berlin JD, Venook A, Bergsland E, Rothenberg M, Lockhart AC, Rosen L. Colorectal Cancer. 2008;7(1): 44-7. doi: 10.3816/CCC.2008.n.006.
Cook L M, Hurst D R, Welch D R. Metastasis suppressors and the tumor microenvironment. Semin Cancer Biol, 2011; 21(2), 113-122. https://doi.org/10.1016/j.semcancer.2010.12.005
Arnold J, David P. The P53 family: a subject collection from cold spring Harbor perspectives in biology laboratory press. Molecular cancer, 2010; 126:273-84.
Yonezawa A, Masuda S, Yokoo S, Katsura T, Inui K. Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family) J. Pharmacol. Exp. Ther. 2006; 19: 879–886. doi:10.1124/jpet.106.110346.
