OBJECTIVE: In this study, the effect of metformin, SB203580, and takinib alone or in combination with radiotherapy on MCF-7 and MDA-MB-231 breast cancer cell lines was evaluated.
METHODS: MCF-7 and MDA-MB-231 breast cancer cell lines were treated with metformin, SB203580, and takinib for 24 or 48 hours, followed by X-ray exposure. The MTT assay and flow cytometry analysis were performed to assess cell growth inhibition and cellular death, CXCr4 expression, and BCSCs, respectively.
RESULTS: The results showed the combination of takinib/SB203580 with radiotherapy to remarkably reduce the CXCR4 expression and BCSCs levels in the MCF-7 cell line. Also, the concurrent administration of takinib/metformin/radiotherapy significantly reduced BCSCs and CXCR4 metastatic markers in the MDA-MB- 231 cells. Since the MAPK signaling pathway has an important role in inducing drug resistance and cell proliferation, the use of SB203580 as an inhibitor of p38 MAPK can improve breast cancer treatment. Furthermore, metformin and ionizing radiation by suppression of the mTOR signaling pathway can control AMPK activation and cellular proliferation.
CONCLUSIONS: Anti-cancer and cytotoxic effects of metformin can be effective in this strategy. In conclusion, the combination of conventional chemotherapeutic drugs, including SB203580, metformin, and takinib with X-ray exposure can be a new approach to diminish the drug resistance of breast cancer.
目的:在本研究中,二甲双胍的作用,对SB203580、单独或联合放疗对MCF-7和MDA-MB-231乳腺癌细胞系进行评价。
方法:用二甲双胍治疗MCF-7和MDA-MB-231乳腺癌细胞系,SB203580和takinib持续24或48小时,其次是X射线曝光。进行MTT分析和流式细胞术分析以评估细胞生长抑制和细胞死亡。CXCr4表达式,和BCSC,分别。
结果:结果显示,在MCF-7细胞系中,他尼/SB203580联合放疗可显著降低CXCR4的表达和BCSC的水平。此外,同时给予他替尼/二甲双胍/放疗可显著降低MDA-MB-231细胞中的BCSC和CXCR4转移标志物.由于MAPK信号通路在诱导耐药和细胞增殖中具有重要作用,使用SB203580作为p38MAPK抑制剂可以改善乳腺癌的治疗。此外,二甲双胍和电离辐射通过抑制mTOR信号通路可以控制AMPK的激活和细胞增殖。
结论:二甲双胍的抗癌和细胞毒性作用在该策略中是有效的。总之,常规化疗药物的组合,包括SB203580,二甲双胍,而X线照射他替尼可以成为降低乳腺癌耐药的新方法。