ABSTRACT
In recent years, salinomycin has been shown to exert an anticancer effect in a variety of tumors; however, its function and mechanism in bladder cancer (BC) remain unclear. This study examined the effect of salinomycin on bladder cancer and analyzed its regulatory mechanism. T24 cells were treated with different concentrations of salinomycin to detect subsequent changes in cell proliferation, apoptosis, oxidative stress, H3K4 methylation, and related gene expression by the CCK8 assay, Edu staining, Tunel staining, ELISA, RT-qPCR, and western blotting, respectively. A KDM1A overexpression plasmid, catalytically inactive KDM1A overexpression plasmid, or short hairpin RNA (shRNA) plasmid was transfected into T24 cells to evaluate their effects. A xenograft tumor model was used to further confirm the anti-tumor effect of salinomycin. Our results showed that salinomycin significantly inhibited cell proliferation, promoted apoptosis, increased MDA levels, decreased SOD levels, induced H3K4 histone methylation, and suppressed KDM1A expression. Furthermore, the sh-KDM1A plasmid had effects similar to those of salinomycin and also activated the unfolded protein response pathway. The KDM1A overexpression plasmid had effects opposite to those of the sh-KDM1A plasmid, and the catalytically inactive KDM1A overexpression plasmid had no effect. Meanwhile, KDM1A overexpression reversed the effects of salinomycin on T24 cells. Finally, in vivo experiments confirmed the above results. In the salinomycin treatment group, tumor growth and KDM1A expression were suppressed and cell apoptosis and UPR were induced, while treatment with the KDM1A overexpression plasmid produced the opposite effects. Collectively, our study revealed that salinomycin suppressed T24 cell proliferation and promoted oxidative stress and apoptosis by regulating KDM1A and the UPR pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00546-y.
ABSTRACT
OBJECTIVE: To investigate the effect of lipid peroxidation on testosterone (T) in the serum and bcl-2 expression in the Leydig cells of aging male rats. METHODS: The D-galactose-induced subacute aging male rat model was established and 20 SD rats were randomly divided into two groups of equal number: a D-galactose (D) group and a control (C) group. The activity of superoxide dismutase(SOD) and the level of malondialdehyde (MDA) were examined by spectro-absorptiometer, the expression of bcl-2 by immunohistochemical method, and the concentration of serum T by radio-immunity technique. RESULTS: (1) The activity of SOD in the testis of the D group was (116 +/- 18.09) U/ mg x prot, significantly lower than in the C group [(156 +/- 31.02) U/mg x prot (P < 0.01)]. (2) The level of MDA in the testis of the D group was (1.77 +/- 0.41) nmol/mg x prot, significantly higher than in the C group [(1.19 +/- 0.15) nmol/mg x prot (P < 0.05)]. (3) Serum T in the D group was (2.39 +/- 0.90) nmol/L, significantly lower than in the C group [(8.95 +/- 2.53) nmol/L (P < 0.01)]. (4) The expressions of bcl-2 in the leydig cells of the D and C groups were (35.1 +/- 3.6)% and (49.6 +/- 7.4)% respectively, with statistical difference between them (P < 0.01). CONCLUSION: Lipid peroxidation affects the concentration of serum T and the expression of bcl-2 in the Leydig cells of aging male rats.
