1.Influence of Co-inhibiting mTORC2 and HSP90 on Proliferation Apoptosis of Multiple Myeloma Cells.
Kan-Kan CHEN ; Yue CHEN ; Zheng-Mei HE ; Li-Tao ZHOU ; Li-Juang ZHANG ; Li-Xiao SONG ; Bang-He DING ; Chun-Ling WANG ; Liang YU ; Jian-Wei ZHOU
Journal of Experimental Hematology 2016;24(4):1086-1090
UNLABELLEDObjective:To explore the influence of co-inhibiting mTORC2 and HSP90 on the proliferation and apoptosis of multiple myeloma(MM) cell line U266.
METHODSDuring culture, the human MM cell line U266 were treated with 20 nmol/L of rapamycin, 600 nmol/L 17-AAG, 20 nmol/L of rapamycin + 600 nmol/L 17-AGG and phosphate-buffered saline (PBS), then the growth inhibition rate, morphologic changes, apoptosis rate and the expression of caspase 3 and ATK protein in U266 cells were compared and analyzed.
RESULTSThe rapamycin and 17-AAG both could inhibit the growth of U266 cells, while the inhibitory effect of rapamycin in combination with 17-AAG on growth of U266 cells was significantly higher them that of rapamycin and 17-AAG alone and control (PBS); the apoptosis rate of U266 cells treated with rapamycin, 17-AAG and their combination was higher than that of control PBS groups, and the efficacy of 2 drug conbination was higher than that of control PBS group, and the efficacy of 2 drug combination was superior to single drug. The expression levels of caspase 3 and ATK in U266 cells treated with rapamycin, 17-AAG and their combination were higher and lower than those in control group respectively, and the efficacy of 2 drug combination was superior to signle drug. There were significant difference between them (P<0.05).
CONCLUSIONThe co-inhibition of mTORC2 and HSP90 can suppress the proliferation and induce the apoptosis of MM cells.
Apoptosis ; Benzoquinones ; Caspase 3 ; Cell Line, Tumor ; Cell Proliferation ; HSP90 Heat-Shock Proteins ; Humans ; Lactams, Macrocyclic ; Mechanistic Target of Rapamycin Complex 2 ; Multiple Myeloma ; Multiprotein Complexes ; Sirolimus ; TOR Serine-Threonine Kinases