Hsp90抑制剂17-AAG通过EGFR,IGFR途径抑制乳腺癌细胞的增殖

 17-AAG通过抑制Hsp90的功能而抑制多种肿瘤细胞的生长增殖,用不同浓度17-AAG作用于乳腺癌细胞株MDA-MB-231和BT474,用SRB法检测细胞相对存活数,计算半数抑制药物浓度IC₅₀;并用Westernblotting检测Hsp90的"顾客"蛋白EGFR,IGFR-1以及G2/M细胞周期蛋白cdc2的表达,研究17-AAG抑制乳腺癌细胞的增殖,促进细胞凋亡的途径.结果显示,1μmol/L的17-AAG已能完全抑制MDA-MB-231和BT474细胞增殖,2种细胞的IC₅₀分别为0.0587,0.0576μmol/L;17-AAG作用的乳腺癌细胞EGFR,IGFR-1表达明显下调,此作用呈剂量依赖性.这些研究结果表明17-AGG可显著抑制乳腺癌细胞MDA-MB-231和BT474的生长增殖,此作用与17-AGG抑制细胞生长因子受体途径有关.

Hsp90 inhibitor,17-AAG,abrogates breast cancer cells growth through EGFR and IGFR-1 pathway

17 -(demethoxy),17-allylamino geldanamycin(17-AAG) suppresses growth in some cancers by inhibiting Heat shock protein90 (Hsp90).We examined in vitro the effects of 17-AAGmediated Hsp90 inhibition on human breast cancer cell lines,MDA-MB -231 and BT474.Cell viabilities were determined by SRBmethod to account IC₅₀; EGFR,IGFR-1 and G2 /Mcell cycle checkpoint proteins cdc2 were examined by Western blotting to determine the pathway of the roles of 17-AAGin breast cancers.We found that MDA-MB-231 and BT474 treated with 17-AAGversus untreated controls showed decreased cell viability.Cells treated with 17-AAGalso showed a decrease in EGFR,IGFR-1.The results suggest that 17-AAGcould obviously abrogate MDA-MB-231 and BT474 cell growth and facilitate the two cell lines apoptosis through EGFRand IGFR-1 pathway.