热休克蛋白90抑制剂17-AAG对HUT-102细胞株JAK3/STAT5信号通路的影响

OBJECTIVE: To analyze whether heat-shock protein 90 (HSP90) be involved in a permanently abnormal activated JAK/STAT signaling in ATL cells in vitro. METHODS: The effect of 17-AAG on proliferation of ATL cell lines HUT-102 was assessed using CCK8 at different time points. Cell apoptosis was measured by flow cytometry. The specific proteins HSP90, STAT5, p-STAT5 and JAK3 were detected by Western blotting. RESULTS: Overexpression of HSP90 in HUT-102 cell lines was disclosed (P<0.05), and constitutive activation of JAK3/STAT5 signaling was observed in HTLV-1-infected T-cell lines but not in normal PBMCs; Treatment of ATL cell lines with 17-AAG led to reduced cell proliferation, but there was no significant change in terms of cell proliferation when the concentration of 17-AAG between 2 000–8 000 nmol/L (P>0.05). 17-AAG induced cell apoptosis in different time-points and concentrations. 17-AAG don't affect the expression of JAK3 gene. CONCLUSION: This study indicated that JAK3 as HSP90 client protein was aberrantly activated in HTLV-1-infected T-cell lines, leading to constitutive activation of p-STAT5 in JAK/STAT signal pathway, which demonstrated that HSP90-inhibitors 17-AAG inhibited the growth of HTLV-1-infected T-cell lines by reducing cell proliferation and inducing cell apoptosis.