CAJ | 학술논문

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.
배경여목적:란소상피성암구유고도침습성,자격소재녀성란소암발생、전이중소기적작용이급종류적전이、침습적궤제연구일익인기국내외관주,골교단백(osteopontin,OPN)시일개중요적추화인자,능촉진세포추화、점부화천이,증가종류세포전이、침습능력,연구발현자격소능통과신호통로영향OPN표체.본실험지재연구자격소대상피성란소암세포전이상관단백OPN적조공작용이급가능적궤제.방법:17-β자이순작용우란소장액성선암세포주SKOV3세포,채용Transwell천막소실체외침습실험관찰종류세포침습능력적변화;채용단백인적법(Western? blot)검측SKOV3세포HIF-1α、OPN단백표체;이CoCl2촉진HIF-1α과표체,이서라막사억제HIF-1α표체후,채용Western? blot방법분별검측자격소작용하OPN단백표체적변화.결과:Transwell소실배양세포24? h,자격소조천과미공막적SKOV3세포수위162±8개,대조조위121±6개,자격소조명현다우대조조(P=0.001).채용Western? blot방법검측,17β자이순촉진SKOV3세포OPN단백급HIF-1α단백표체(P=0.002,P=0.001).촉진HIF-1α과표체후,자격소대SKOV3세포OPN단백표체승조절작용증강(P=0.005);서라막사억제HIF-1α표체후,자격소대SKOV3세포OPN단백표체승조절작용감약(P=0.011).결론:자격소통과HIF-1α조공상피성란소암세포전이상관단백OPN적표체.
?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 17β estradiol. The invasion ability of tumor cells was detected by Transwell chambers. HIF-1αand OPN expression was measured by Western blot. The change of OPN expression when HIF-1α was over-expressed by CoCl2 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±8, significantly elevated (P=0.001), compared with vehicle. Western blot result showed that 17β estradiol increased expression of HIF-1α and OPN (P=0.002, P=0.001). When SKOV3 cells were transfected by CoCl2 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.