Impact of Combination Therapy with Chemical Drugs and Megavoltage X-ray Exposure on Breast Cancer Stem Cells’ Viability and Proliferation of MCF-7 and MDA-MB-231 Cell Lines

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current pharmaceutical design Pub Date : 2024-04-27 DOI:10.2174/0113816128287325240329085055

Fatemeh Banisharif Dehkordi, Mahdi Ghatrehsamani, Maryam Abdolvand, Amin Soltani, Seyed Hossein Masoumi

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引用次数: 0

Abstract

Background:: 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. 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. Conclusion:: 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.

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化学药物联合疗法和巨电压 X 射线照射对 MCF-7 和 MDA-MB-231 细胞株乳腺癌干细胞活力和增殖的影响

背景乳腺癌（BC）是女性中一种严重的恶性肿瘤。化疗是治疗癌症的重要手段，但长期使用化疗药物可能导致耐药性和肿瘤复发。由于乳腺癌干细胞（BCSCs）是诱导乳腺癌耐药和复发的主要因素，因此研究BCSCs信号通路是提高癌症治疗效率的有效方法。研究目的本研究评估了二甲双胍、SB203580、他克尼单独或联合放疗对MCF-7和MDA-MB-231乳腺癌细胞系的影响。方法：：用二甲双胍、SB203580 和他替尼处理 MCF-7 和 MDA-MB-231 乳腺癌细胞株 24 或 48 小时，然后进行 X 射线照射。分别用 MTT 试验和流式细胞术分析评估细胞生长抑制和细胞死亡、CXCr4 表达和 BCSCs。结果显示结果显示，他克尼/SB203580联合放疗可显著降低MCF-7细胞系的CXCR4表达和BCSCs水平。同时服用他克尼/二甲双胍/放疗还能显著减少MDA-MB- 231细胞中的BCSCs和CXCR4转移标记物。由于 MAPK 信号通路在诱导耐药性和细胞增殖方面起着重要作用，因此使用 SB203580 作为 p38 MAPK 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。结论在这一策略中，二甲双胍的抗癌和细胞毒性作用可发挥有效作用。总之，将SB203580、二甲双胍、他克尼等传统化疗药物与X射线照射相结合，可以成为减少乳腺癌耐药性的一种新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current pharmaceutical design 医学-药学

CiteScore

6.30

自引率

0.00%

发文量

302

审稿时长

2 months

期刊介绍： Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field. Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism.