Effects of Artesunate Combined with Arsenious Acid on Proliferation and Apoptosis of Multiple Myeloma Cells via PI3K/AKT Signaling Pathway

Abstract

To investigate the effect of artesunate and arsenous acid and their combination on the proliferation and apoptosis of human multiple myeloma cells and their mechanism. Human multiple myeloma cell line RPMI 8226 cells were cultured and treated with 0, 1, 2, 4, 8 nmol/L arsenous acid and 0, 40, 80, 160, 320 μmol/L artesunate, respectively. The inhibition of cell growth was detected by CCK-8 assay. The apoptosis rate was detected by flow cytometry. QPCR was used to detect the mRNA expression of cell proliferation and apoptosis-related factors. The expression of cell proliferation, apoptosis-related factors and PI3K/AKT pathway protein were detected by Western blot. CCK-8 assay showed that the growth of multiple myeloma cells was inhibited by arsenous acid and artesunate. The IC50 of arsenous acid was 1.96 nmol/L, and artesunate was 153.96 μmol/L. Flow cytometry showed that arsenous acid, artesunate, and their combination could significantly increase the apoptosis of multiple myeloma cells. QPCR and Western blot showed that the arsenous acid, artesunate, and their combination treatment could inhibit the expression of mRNA and protein of cell proliferation-related factors interleukin-6 and vascular endothelial growth factor (P<0.05), inhibit apoptosis-related factor BCL-xl and promote the expression of mRNA and protein of Bax (P<0.05), and reduce the protein expression of p-PI3K and p-AKT in PI3K/AKT signaling pathway (P<0.05). Moreover, the combination effect of the two drugs on cell apoptosis and the above mentioned factors was obviously stronger than that of the two drugs alone. Artesunate combined with arsenous acid inhibits proliferation and promotes apoptosis of tumor cells through PI3K/AKT signaling pathway, and is superior to the effect of two drugs alone.