CAJ | 학술논문

目的：探讨苯醌类安沙霉素药物17AAG对胃癌细胞增殖和侵袭能力的影响及其作用机制。方法17AAG作用于胃癌细胞SGC7901后，应用MTT法检测细胞增殖能力的变化；应用流式细胞术检测细胞周期的改变；应用流式细胞术和PI/Annexin Ⅴ双染色法检测细胞凋亡情况；应用Transwell实验检测细胞侵袭能力的变化；应用Western blot法检测热休克蛋白（HSP90和HSP70）及其客户蛋白（c-met和AKT）表达的改变。结果17AAG作用后，胃癌细胞SGC7901生长明显受抑，且该抑制作用呈剂量和时间依赖性；细胞周期被阻滞于G0/G1期；与空白对照组和DMSO对照组比较，17AAG处理组细胞凋亡率显著升高（P＜0．01）；侵袭能力显著下降（P＜0．01）。17AAG可上调HSP70的表达，下调HSP90客户蛋白c-met和AKT的表达，但HSP90表达无明显变化。结论17AAG对胃癌细胞SGC7901具有抑制增殖、诱导凋亡和降低侵袭能力的作用，该作用并不是通过其靶点HSP90，而是通过下调HSP90客户蛋白的表达而实现的。
목적：탐토분곤류안사매소약물17AAG대위암세포증식화침습능력적영향급기작용궤제。방법17AAG작용우위암세포SGC7901후，응용MTT법검측세포증식능력적변화；응용류식세포술검측세포주기적개변；응용류식세포술화PI/Annexin Ⅴ쌍염색법검측세포조망정황；응용Transwell실험검측세포침습능력적변화；응용Western blot법검측열휴극단백（HSP90화HSP70）급기객호단백（c-met화AKT）표체적개변。결과17AAG작용후，위암세포SGC7901생장명현수억，차해억제작용정제량화시간의뢰성；세포주기피조체우G0/G1기；여공백대조조화DMSO대조조비교，17AAG처리조세포조망솔현저승고（P＜0．01）；침습능력현저하강（P＜0．01）。17AAG가상조HSP70적표체，하조HSP90객호단백c-met화AKT적표체，단HSP90표체무명현변화。결론17AAG대위암세포SGC7901구유억제증식、유도조망화강저침습능력적작용，해작용병불시통과기파점HSP90，이시통과하조HSP90객호단백적표체이실현적。
Objective To investigate the effect of 17-allylamino-demethoxygeldanamycin (17AAG) on the proliferative and invasive ability of gastric cancer cells and associated mechanism. Methods The proliferative ability was tested by MTT method and the cell cycle was detected by flow cytometry (FCM) when 17AAG was used to treat gastric cancer cell SGC7901. Apoptosis was detected by FCM and PI-Annexin V double staining. The invasive ability was tested by transwell method. Expression of HSP90, HSP70, c-met and AKT was detected by Western blot. Results The growth of SGC7901 cells was inhibited after the administration of 17AAG, and the inhibitation was dose- and time-dependent. The cell cycle was blocked at the G0/G1 phase. The apoptotic ratio in 17AAG group was much higher than that in blank group and DMSO group (P<0.01). The cellular invasive ability decreased significantly (P<0.01). The expression of HSP70 was elevated by 17AAG, and the expression of c-met and AKT was down-regulated, but no change of HSP90 was observed. Conclusion 17AAG can inhibit the proliferative and invasive ability of SGC7901 cells , and induces apoptosis through down-regulating the expression of HSP90 client proteins instead of the target HSP90 itself.