TNFα刺激的间充质干细胞对乳腺癌细胞化疗敏感性的影响
首发时间:2019-06-03
摘要:探讨间充质干细胞(MSCs)以及TNFα刺激的间充质干细胞在乳腺癌化疗耐受中的作用及其机制。方法:通过流式鉴定MSCs的表面标记;利用CCK8检测阿霉素(DOX)对4T1肿瘤细胞的杀伤作用;使用Annexin V凋亡试剂盒检测4T1的凋亡情况;RT-qPCR检测4T1细胞以及MSCs的趋化因子和凋亡相关基因的表达。结果:TNFα刺激的MSCs不能进一步引起乳腺癌对DOX的化疗耐受,但是能分泌更多的趋化因子CCL8。结论:在体外条件下,TNFα刺激的MSCs在体外虽然不能进一步引起乳腺癌的化疗耐受,但是在体内可能通过分泌更多的趋化因子改变肿瘤微环境,更进一步地促进肿瘤化疗耐受。
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Modulation of the chemoresistant effect of mesenchymal stromal cells conferred to breast cancer cells by TNFα treatment
Abstract:Objective: To investigate the role and mechanism of mesenchymal stem cells (MSCs) and TNFα-stimulated MSCs in the chemoresistance of breast cancer. Methods: The surface markers of MSCs were identified by flow cytometry; the cytotoxic effect of doxorubicin (DOX) on 4T1 cells was measured by CCK8; the apoptosis of 4T1 was determined by Annexin V apoptosis kit; RT-qRCR was used to detect the expression of chemokines and apoptosis-related genes in 4T1 cells and MSCs. Results: Bone marrow-derived MSCs can confer breast cancer cells resistance to DOX regardless of TNFα treatment. The expression of CCL8 is greatly upregulated by the combined TNFα and DOX treatment. Conclusion: TNFα treatment does not confer breast cancer cells increased chemoresistance in vitro, but TNFα-stimulated MSCs could further promote tumor chemoresistance in vivo by remodeling tumor microenvironment via their secretome.
Keywords: mesenchymal stem cells breast cancer chemotherapy resistance doxorubicin
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TNFα刺激的间充质干细胞对乳腺癌细胞化疗敏感性的影响
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