Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Microbiology and Immunology, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Curr Pharm Des. 2024;30(17):1341-1353. doi: 10.2174/0113816128287325240329085055.
Breast Cancer (BC) is a serious malignancy among women. However, chemotherapy is an important tool for cancer treatments, but the long-term use of chemotherapy drugs may lead to drug resistance and tumor recurrence. Since Breast Cancer Stem Cells (BCSCs) can be the main factor to induce BC treatment resistance and recurrence, investigation of BCSCs signaling pathways can be an effective modality to enhance cancer treatment efficiency.
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.
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.
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.
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.
乳腺癌（BC）是女性中的一种严重恶性肿瘤。然而，化疗是癌症治疗的重要手段，但长期使用化疗药物可能导致耐药和肿瘤复发。由于乳腺癌干细胞（BCSCs）可能是诱导 BC 治疗耐药和复发的主要因素，因此研究 BCSCs 信号通路可以成为提高癌症治疗效果的有效方式。
本研究评估了二甲双胍、SB203580 和替尼布单独或与放疗联合应用于 MCF-7 和 MDA-MB-231 乳腺癌细胞系的效果。
用二甲双胍、SB203580 和替尼布处理 MCF-7 和 MDA-MB-231 乳腺癌细胞系 24 或 48 小时，然后进行 X 射线照射。采用 MTT 法和流式细胞术分别检测细胞生长抑制和细胞死亡、CXCr4 表达和 BCSCs。
结果表明，替尼布/SB203580 与放疗联合显著降低 MCF-7 细胞系中 CXCR4 表达和 BCSCs 水平。此外，替尼布/二甲双胍/放疗同时给药可显著降低 MDA-MB-231 细胞中的 BCSCs 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，因此使用 SB203580 作为 p38 MAPK 的抑制剂可以改善乳腺癌的治疗效果。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 激活和细胞增殖。
二甲双胍的抗癌和细胞毒性作用在该策略中可能是有效的。总之，将常规化疗药物（包括 SB203580、二甲双胍和替尼布）与 X 射线照射联合使用可能是减少乳腺癌耐药性的新方法。
