Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells
作者： MASAKI MORI , TOSHIAKI HITORA , OSAMU NAKAMURA , YOSHIKI YAMAGAMI , RYOSUKE HORIE
关键词: PI3K/AKT/mTOR pathway 、 Geldanamycin 、 Cell growth 、 Hsp90 inhibitor 、 Programmed cell death 、 Apoptosis 、 Cell biology 、 Protein kinase B 、 Cancer research 、 Biology 、 Autophagy
摘要: Heat shock protein 90 (Hsp90) is constitutively expressed at 2-10-fold higher levels in tumor cells compared to normal cells, suggesting that it may be critically important for cell growth and survival. These features make Hsp90 a potential target anticancer drug development. Inhibition of activity not only results rapid degradation client proteins but also induces apoptosis various cells. plays an role autophagy. An inhibitor autophagy through inhibition mTOR. It still under debate whether chemotherapy-induced protective response or invoked promote death. The aim this study was examine the effects inhibitor, geldanamycin (GA), on KTHOS osteosarcoma We further examined combination GA 3-methyl-adenine (3-MA) enhanced GA-induced had inhibitory effect proliferation inhibited Akt/mTOR signaling pathway alone induced treatment with 3-MA suppressed much greater extent than these considered mechanism by apoptosis. Therefore, effective because effectively apoptotic pathways.
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