Abstract: Objective To investigate the effects of protein phosphatase 2 regulatory subunit B'gamma (PPP2R5C) on the proliferation, apoptosis and drug sensitivity of multiple myeloma (MM) cells. Methods The qRT⁃PCR and Western blot were used to detect the expression of PPP2R5C in human multiple myeloma cell lines (MM1S and RPMI⁃8226 cell lines) and normal peripheral blood mononuclear cells(PBMC). The MM1S cells were transfected with PPP2R5C interfering siRNA (si⁃PPP2R5C group) and its negative control (si⁃CTRL group), and PPP2R5C overexpressing plasmid (OE⁃PPP2R5C group) and its negative control (OE⁃CTRL group), respectively. Cell proliferation was detected by CCK⁃8 method, and cell apoptosis was detected by flow cytometry. The cells in the si⁃PPP2R5C group and si⁃CTRL group were treated with different concentrations of Bortezomib (BTZ) for 24 h, cell viability was measured by CCK⁃8 method and half maximal inhibitory concentration (IC₅₀) values were calculated. After 1 nmol/L BTZ intervention for 24 h, the expression levels of BCL⁃2 and BAX in the si⁃PPP2R5C and si⁃CTRL groups were detected by qRT⁃PCR and Western blot, and Caspase⁃3/7 activity was detected by Caspase 3/7 activity detection kit, and cell apoptosis was detected by flow cytometry. Results Compared with PBMC cells, PPP2R5C was highly expressed in MM1S and RPMI⁃8226 cells at both mRNA and protein levels (all P<0.001). Compared with the si⁃CTRL group, the cell proliferation activity of si⁃PPP2R5C group was inhibited after 48 h and 72 h of cell culture (all P<0.001), the apoptosis rate was significantly increased (5.97% vs 14.39%, P<0.001). Compared with the OE⁃CTRL group, the cell proliferation activity of OE⁃PPP2R5C group was enhanced at these time points after 48 h and 72 h of cell culture (all P<0.01). The IC₅₀ value of BTZ in the si⁃PPP2R5C group was significantly lower than that in the si⁃CTRL group(3.40 nmol/L vs 10.37 nmol/L, P<0.001). Moreover, compared with the control group and si⁃CTRL+BTZ group, mRNA and protein level of BCL⁃2 in the si⁃PPP2R5C+BTZ group were decreased, while the mRNA and protein level of BAX, Caspase 3/7 activity and cell apoptosis rate were increased (all P<0.05).Conclusions PPP2R5C is highly expressed in MM cell lines. PPP2R5C knockdown can inhibit the cell proliferation and promote apoptosis of MM cells, and increase the drug sensitivity of BTZ.

Key words: Multiple myeloma, PPP2R5C, Proliferation, Apoptosis, Drug resistance