摘要
背景与目的:卵巢上皮性癌具有高度侵袭性,雌激素在女性卵巢癌发生、转移中所起的作用以及肿瘤的转移、侵袭的机制研究日益引起国内外关注,骨桥蛋白(osteopontin,OPN)是一个重要的趋化因子,能促进细胞趋化、粘附和迁移,增加肿瘤细胞转移、侵袭能力,研究发现雌激素能通过信号通路影响OPN表达。本实验旨在研究雌激素对上皮性卵巢癌细胞转移相关蛋白OPN的调控作用以及可能的机制。方法:17-β雌二醇作用于卵巢浆液性腺癌细胞株SKOV3细胞,采用Transwell穿膜小室体外侵袭实验观察肿瘤细胞侵袭能力的变化;采用蛋白印迹法(Western blot)检测SKOV3细胞HIF-1α、OPN蛋白表达;以CoCl2促进HIF-1α过表达,以西罗莫司抑制HIF-1α表达后,采用Western blot方法分别检测雌激素作用下OPN蛋白表达的变化。结果:Transwell小室培养细胞24 h,雌激素组穿过微孔膜的SKOV3细胞数为162±8个,对照组为121±6个,雌激素组明显多于对照组(P=0.001)。采用Western blot方法检测,17β雌二醇促进SKOV3细胞OPN蛋白及HIF-1α蛋白表达(P=0.002,P=0.001)。促进HIF-1α过表达后,雌激素对SKOV3细胞OPN蛋白表达升调节作用增强(P=0.005);西罗莫司抑制HIF-1α表达后,雌激素对SKOV3细胞OPN蛋白表达升调节作用减弱(P=0.011)。结论:雌激素通过HIF-1α调控上皮性卵巢癌细胞转移相关蛋白OPN的表达。
Background and purpose: Estrogen has played an important role in the metastasis of epithelial ovarian cancer. Researches have revealed estrogen may regulate osteopontin (OPN), a chemokine, to increase the invasion ability of cancer cells by signal pathway. This study is to assess estrogen's regulation on the expression of metastasis related protein OPN in epithelial ovarian cancer. Methods: Ovarian serous adenocarcinoma cell line SKOV3 was treated by 1713 estradiol. The invasion ability of tumor cells was detected by Transwell chambers. HIF-1α and OPN expression was measured by Western blot. The change of OPN expression when HIF-1α was over-expressed by CoC12 or suppressed by Sirolimus was measured by Western blot. Results: SKOV3 cells were cultured in transwell after 24 hours. The invasion of cells treated with estrogen was 162-4-8, significantly elevated (P=-0.001), compared with vehicle. Western blot result showed that 17β estradiol increased expression of HIF-lct and OPN (P=-0.002, P=-0.001). When SKOV3 cells were transfected by CoC12 which over-expressed HIF-1α, the effects of estrogen on OPN expression were attenuated (P=0.005). When SKOV3 cells were transfected by Sirolimus which suppressed HIF-1α, the effects of estrogen on OPN expression were accenuated (P=0.011). Conclusion: Estrogen can affect the expression of OPN by regulating HIF-1α.
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2012年第11期814-819,共6页
China Oncology