论文部分内容阅读
目的探讨人骨髓间充质干细胞(BMSCs)耐受化疗药物损伤的作用机制。方法分离培养人BMSCs;用免疫荧光等方法检测体外培养的BMSCs对3种化疗药物顺铂、长春新碱和喜树碱处理后的反应;分析凋亡诱导基因家族p53和p73的表达情况。结果与敏感的肿瘤细胞系K562相比,体外培养BMSCs对3种化疗药物有较高的耐受性;临床剂量的化疗药物处理后,细胞的表型、增殖和分化及衰老指标均无改变;与敏感的肿瘤细胞系K562相比,亚凋亡剂量化疗药物的处理导致BMSCs内出现与凋亡诱导无关的p53表达增高;BMSCs内p73的表达量明显低于K562细胞系,且药物的处理未能改变其表达水。结论体外培养的BMSCs能耐受多种化疗药物的促凋亡作用并在药物处理结束后仍保持其干细胞的特性;BMSCs的抗损伤状态可能与细胞内低水平的p73表达量有关;p73蛋白可能在BMSCs抗损伤调节中具有重要的作用。
Objective To investigate the mechanism of human bone marrow mesenchymal stem cells (BMSCs) resistance to chemotherapy drug injury. METHODS: Human BMSCs were isolated and cultured. The response of BMSCs cultured in vitro to cisplatin, vincristine and camptothecin were detected by immunofluorescence. The expressions of p53 and p73 in apoptosis-inducing gene family were analyzed. Results Compared with the sensitive tumor cell line K562, BMSCs cultured in vitro were highly tolerant to three chemotherapeutic drugs. No change was observed in the phenotype, proliferation, differentiation and senescence of the cells after treatment with the chemotherapeutic drugs in clinical dose. Compared with the sensitive tumor cell line K562, treatment with sub-apoptotic doses of chemotherapeutic agents resulted in increased expression of p53 in BMSCs that was not associated with induction of apoptosis; p73 expression was significantly lower in BMSCs than in K562 cells, and treatment with the drug Can change its expression of water. CONCLUSION: BMSCs cultured in vitro are able to tolerate various chemotherapeutic drugs and maintain the characteristics of stem cells after the drug treatment. The anti-injury status of BMSCs may be related to the low level of intracellular p73 expression. P73 protein may Plays an important role in anti-injury regulation of BMSCs.