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目的 :本项目旨在探讨在体外实验中洛伐他汀(Lovastatin,LV)是否能够通过增加对化疗药物的敏感性而提高对乳腺癌细胞的杀伤效果。方法 :采用超低粘附悬浮培养法从MDA-MB-231细胞获得乳腺癌干细胞样细胞。用LV加或不加化疗药物在缺氧条件下对细胞进行处理。用流式细胞仪检测细胞凋亡,用化学发光法检测细胞Caspase 3/7活性,用MTT法检测细胞增殖活性。结果 :单独使用时,LV能够显著促进MDA-MB-231细胞的凋亡并增加Caspase 3/7活性,而对ER阳性的MCF-7作用不明显。与化疗药物多柔比星联合使用时,LV显著增加乳腺癌干细胞对多柔比星的敏感性。结论 :天然化合物LV在体外能够促进乳腺癌细胞凋亡并增加乳腺癌干细胞对化疗药物多柔比星的敏感性。上述研究结果为设计针对乳腺癌的治疗方案提供了一种可能的选择,其体内作用仍需进一步研究证实。
Objectives: This study aimed to investigate whether in vitro experiments whether lovastatin (LV) increases the cytotoxicity of breast cancer cells by increasing the sensitivity to chemotherapy drugs. Methods: Breast cancer stem cell-like cells were obtained from MDA-MB-231 cells by ultra-low adhesion suspension culture. Cells were treated under hypoxic conditions with or without chemotherapy with or without LV. Cell apoptosis was detected by flow cytometry. Caspase 3/7 activity was detected by chemiluminescence assay and cell proliferation activity by MTT assay. Results: When used alone, LV could significantly promote the apoptosis of MDA-MB-231 cells and increase the activity of Caspase 3/7, but not to ER-positive MCF-7. When used in combination with the chemotherapeutic drug doxorubicin, LV significantly increases the sensitivity of breast cancer stem cells to doxorubicin. Conclusion: The natural compound LV can promote breast cancer cell apoptosis in vitro and increase the sensitivity of breast cancer stem cells to chemotherapeutic drug doxorubicin. The above findings provide a possible alternative for the design of a therapeutic regimen for breast cancer, and its efficacy in vivo remains to be confirmed by further studies.