CAJ | 학술논문

目的探讨17-AAG增加TRAIL诱导肝癌细胞HepG2凋亡的分子机制.方法应用流式细胞仪分析17-AAG联用TRAIL对肝癌细胞HepG2细胞周期的影响;Western blot检测HepG2细胞在17-AAG作用前后凋亡信号传导蛋白Caspase-8、caspa8e-3、c-FLIP、RIP及NF-KB上游调节激酶Akt、IKb-α蛋白的表达变化.结果联合用药组的细胞生存率为(17.25±2.34)%,显著低于17-AAG单独用药组的[(93.14±5.25)%,P<0.01];17-AAG预处理,随其浓度和时间的增加能明显下调RIP的表达,进而影响Akt的磷酸化,但对c-FLIP的表达无明显影响.结论 TRAIL联合17-AAG可以诱导肝癌细胞凋亡,其机制是通过下调RIP的表达,活化凋亡发生的死亡受体通路及阻断NF-κB通路来实现的.
목적 탐토17-AAG증가TRAIL유도간암세포HepG2조망적분자궤제.방법 응용류식세포의분석17-AAG련용TRAIL대간암세포HepG2세포주기적영향;Western blot검측HepG2세포재17-AAG작용전후조망신호전도단백Caspase-8、caspa8e-3、c-FLIP、RIP급NF-KB상유조절격매Akt、IKb-α단백적표체변화.결과 연합용약조적세포생존솔위(17.25±2.34)%,현저저우17-AAG단독용약조적[(93.14±5.25)%,P<0.01];17-AAG예처리,수기농도화시간적증가능명현하조RIP적표체,진이영향Akt적린산화,단대c-FLIP적표체무명현영향.결론 TRAIL연합17-AAG가이유도간암세포조망,기궤제시통과하조RIP적표체,활화조망발생적사망수체통로급조단NF-κB통로래실현적.
Objective To investigate the synergistic molecular mechanism of 17-allylamino-17-demethoxy-geldanamycin (17-AAG) enhancing the TRAIL-induced apoptosis of HepG2 of hepatocellular carcinoma cell lines. Methods Flow cytometry was used to analyze the effects of co-treatment of 17-AAG and TRAIL on the HepG2 cell cycle. The expression of Caspase-8, Caspase-3, c-FLIP, RIP, Akt and IKb-α was detected by Western blot before and after the treatment with 17-AAG. Results The cell viability of HepG2 was (17.25±2.34) % in co-treated groups, significantly lower than (93.14±5.25) % in 17-AAG groups (P < 0.01). Pretreatment with 17-AAG could downregulate the expression of RIP and influ-ence the phosphorylation of Akt with the increases of concentration and time, but had no significant effect on the expression of c-FLIP. Conclusion 17-AAG could sensitize HepG2 ceils to TRAIL-induced apopto-sis by downregulating the expression of RIP,activating the death receptor pathway and blocking the NF-KB pathway.