【摘要】：目的:研究腺苷酸活化蛋白激酶(AMPK)激活與卵巢癌細(xì)胞對(duì)順鉑耐藥的關(guān)系。方法:以不同濃度的順鉑(0,3.125,6.25,12.5,25,50μmol·L-1)分別作用人卵巢癌細(xì)胞SKOV3及其順鉑耐藥株SKOV3/DDP 24h,MTT法檢測(cè)順鉑的抑制率;透射電鏡檢測(cè)SKOV3和SKOV3/DDP中的自噬體;流式細(xì)胞術(shù)檢測(cè)順鉑作用SKOV3和SKOV3/DDP的凋亡率;Western blot法測(cè)定基礎(chǔ)狀態(tài)下及順鉑單獨(dú)或聯(lián)合AMPK抑制劑compound C作用時(shí),SKOV3和SKOV3/DDP中p-AMPK、自噬微管相關(guān)蛋白輕鏈3(LC3-Ⅱ)和凋亡蛋白聚腺苷二磷酸-核糖聚合酶(PARP)的表達(dá)差異;并測(cè)定compound C聯(lián)合順鉑作用SKOV3和SKOV3/DDP時(shí)的細(xì)胞活性。結(jié)果:與SKOV3比較,SKOV3/DDP對(duì)順鉑耐藥(RI=6.8);SKOV3/DDP中自噬體明顯增多(P0.01);順鉑對(duì)SKOV3/DDP早期凋亡率(7.0±0.55)%遠(yuǎn)低于SKOV3早期凋亡率(30.5±0.34)%(P0.01);SKOV3/DDP中p-AMPK、LC3-Ⅱ表達(dá)量均增加,順鉑作用時(shí)Cleaved-PARP表達(dá)不明顯;compound C與順鉑同時(shí)作用時(shí),SKOV3/DDP中p-AMPK、LC3-Ⅱ表達(dá)減少,Cleaved-PARP表達(dá)水平顯著升高,且SKOV3/DDP對(duì)順鉑敏感性增加。結(jié)論:SKOV3/DDP中p-AMPK的激活誘導(dǎo)卵巢癌細(xì)胞自噬可能導(dǎo)致其對(duì)順鉑耐藥,compound C抑制p-AMPK的激活,與順鉑同時(shí)作用促進(jìn)順鉑誘導(dǎo)SKOV3/DDP細(xì)胞凋亡,且增加其對(duì)順鉑的敏感性。
[Abstract]:Aim: to study the relationship between adenylate activated protein kinase (AMPK) activation and cisplatin resistance in ovarian cancer cells. Methods: the inhibition rate of cisplatin was detected by different concentrations of cisplatin (03.125 Cisplatin 6.255.12.5U 2550 渭 mol L-1) on human ovarian cancer cell line SKOV3 and cisplatin resistant cell line SKOV3/DDP for 24 h, and the autophagy in SKOV3 and SKOV3/DDP was detected by transmission electron microscope (TEM). Detection of apoptosis rate of SKOV3 and SKOV3/DDP induced by Cisplatin by flow Cytometry and Western blot Assay for p-AMPK, LC3- 鈪，

本文編號(hào)：2229557