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在前期研究中,YSY-01A通过抑制蛋白酶体活性,对多种肿瘤细胞表现出增殖抑制作用。但是,YSY-01A对于与蛋白酶体途径有着密切联系的自噬系统的影响目前还不清楚。本文研究目的是探讨YSY-01A对自噬的影响与分子机制。研究结果表明,YSY-01A能够显著抑制PC-3M细胞的增殖(P<0.001,IC50=287 nM,48 h),并且该抑制作用具有时间依赖性与浓度依赖性。YSY-01A(400 nM)能够在短时间内诱导PC-3M细胞自噬,12 h后自噬活动步入末期。分子实验结果表明,YSY-01A能够明显促进P53蛋白的磷酸化、抑制mTOR的活化,上调Beclin-1与LC3的表达。而在抑制自噬后,可增加PC-3M细胞对YSY-01A的敏感性。总之,YSY-01A可抑制PC-3M细胞增殖,并能够诱导PC-3M细胞自噬,自噬在12 h后步入末期,抑制自噬后,可增强YSY-01A对PC-3M细胞的增殖抑制作用。
In previous studies, YSY-01A showed inhibitory effects on various tumor cells by inhibiting proteasome activity. However, the effect of YSY-01A on the autophagy system that is closely associated with the proteasomal pathway is unclear. The purpose of this study is to investigate the effect and molecular mechanism of YSY-01A on autophagy. The results show that YSY-01A can significantly inhibit the proliferation of PC-3M cells (P <0.001, IC50 = 287 nM, 48 h), and the inhibition is time-dependent and concentration-dependent. YSY-01A (400 nM) induced autophagy in PC-3M cells in a short period of time, after 12 h, the autophagic activity entered the final stage. The results of molecular experiments showed that YSY-01A can significantly promote the phosphorylation of P53, inhibit the activation of mTOR and up-regulate the expression of Beclin-1 and LC3. In the inhibition of autophagy, PC-3M cells can increase the sensitivity of YSY-01A. In conclusion, YSY-01A could inhibit the proliferation of PC-3M cells and induce the autophagy of PC-3M cells. After autophagy, YSY-01A reached its final stage after 12 hours and inhibited the autophagy. Inhibition.