索拉菲尼对骨肉瘤细胞的抑制作用及分子机制研究

Anti-proliferative effect and mechanisms of sorafenib on osteosarcoma

目的研究索拉菲尼对骨肉瘤细胞增殖和凋亡的作用及其分子机制。方法将人骨肉瘤细胞(HOS细胞)分为对照组及索拉菲尼组,用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐比色法观察索拉菲尼对HOS细胞活力的影响,用蛋白质印迹法检测凋亡相关蛋白变化,用Real-time PCR检测let-7d变化情况。结果索拉菲尼可抑制HOS细胞活力,并呈剂量和浓度依赖性;同时,索拉菲尼可以抑制Lin28表达,同时促进let-7d表达;过表达Lin28可以逆转索拉菲尼的促凋亡作用。结论索拉菲尼通过调控Lin28/le-7d环路来促进骨肉瘤细胞凋亡。

Objective To investigate the pro- apoptotic effect and mechanism of sorafenib on osteosareoma. Methods HOS cells was divi- ded into control group and sorafenib group. 3 - （4,5 - dimethyl - 2 - thiazolyl） -2,5 - diphenyl - 2 - H - tetrazolium bromide （MTF） assay was chosen to investigate the effect of sorafenib on cell viability. Western blot was applied to detect the expression of proteins, and real - time RT- PCR were used to detect the expression of mRNAs. Results The results of MTr assay showed that sorafenib inhibit the proliferation of HOS cells in an dose - and time -dependent manner. Sorafenib induced the inhibition of lin - 28 and increase of let - 7d. Further study showed that Lin28 could attenuate the pro - apoptotic effect of sorafenibin HOS cells. Conclusion Sorafenib induces apoptosis of HOS cells by disrup- ting Lin28/let- 7d feedback.