Analysis of hypoxia-inducible factors in ovarian tumors focusing on individual-based treatment

依维莫司（雷帕霉素的衍生物）处理的细胞和未处理的细胞在mTOR表达上没有任何差异。但磷酸化mTOR（p-mTOR）在处理后的细胞中表达明显降低，mTOR下游区磷酸化4e - bp1 （p-4E-BP1）、HIF-1α、血管内皮生长因子（VEGF）等mTOR相关因子表达明显降低。药物对hif -1α降解系统的影响分析显示，治疗后细胞中VHL表达增加。cleaved caspase-3是参与细胞凋亡的关键因子之一，在处理后的细胞中也显示出增加。在下一步中，使用植入RMG-1细胞的裸鼠，在口服依维莫司的7只小鼠中，有4只小鼠的肿瘤大小减小。结果表明，依维莫司政府将不仅可以通过下调p-mTOR，还可以通过VHL降解hif -1α，通过裂解caspase-3诱导细胞凋亡，从而起到抗CCA的作用。

Everolimus(a derivative of rapamycin)-treated cells and non-treated cells were found not to show any difference in mTOR expression. But, phosphorylated-mTOR(p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1(p-4E-BP1), HIF-1α, and vascular endothelial growth factor(VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1αdegradation system showed an increase in von-Hippel Lindau(VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1αby VHL and induction of apoptosis by cleaved caspase-3.