| 新型蛋白酶体抑制剂 YSY-01A诱导PC-3M细胞自噬的作用 |
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| 引用本文： | 王喆,;袁霞,;葛泽梅,;冉福香,;吴军,;李润涛,;崔景荣.新型蛋白酶体抑制剂 YSY-01A诱导PC-3M细胞自噬的作用[J].中国药学,2014,23(8):565-571. |
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| 作者姓名： | 王喆 ;袁霞 ;葛泽梅 ;冉福香 ;吴军 ;李润涛 ;崔景荣 |
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| 作者单位： | [1]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191; [2]北京大学医学部药学院化学生物学系,北京100191 |
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| 基金项目： | This research was supported by the Eleventh Five-Year Plan for National Science and Technology Major Project （Grant No. 2009ZX0930-010）, National Science Foundation of China （Grant No. 81172915） and a grant from Major New Drugs Research and Development Platform of Peking University （Grant No. 2009ZX- 09301-010）.
Foundation items： Eleventh Five-Year Plan for National Science and Technology Major Project （Grant No. 2009ZX0930-010）, National Science Foundation of China （Grant No. 81172915） and a grant from Major New Drugs Research and Development Platform of Peking University （Grant No. 2009ZX09301-010）. |
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| 摘 要： | 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，48h），并且该抑制作用具有时间依赖性与浓度依赖性。YSY-01A（400nM）能够在短时间内诱导PC．3M细胞自噬，12h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JPC-3M细胞对YSY．01A的敏感性。总之，YSY-01A可抑Nec-3M细胞增殖，并能够诱导PC-3M细胞自噬，自噬在12h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。
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| 关 键 词： | 蛋白酶体抑制剂 YSY-01A PC-3M 自噬 |
A new proteasome inhibitor YSY-01A induced autophagy in PC-3M cells |
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| Zhe Wang,Xia Yuan,Zemei Ge,Fuxiang Ran,Jun Wu,Runtao Li,Jingrong Cui.A new proteasome inhibitor YSY-01A induced autophagy in PC-3M cells[J].Journal of Chinese Pharmaceutical Sciences,2014,23(8):565-571. |
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| Authors: | Zhe Wang Xia Yuan Zemei Ge Fuxiang Ran Jun Wu Runtao Li Jingrong Cui |
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| Affiliation: | Zhe Wang, Xia Yuan, Zemei Ge, Fuxiang Ran, Jun Wu, Runtao Li, Jingrong Cui( 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China 2. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China) |
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| Abstract: | YSY-01A has shown proliferation inhibitory activity to certain types of tumor cells by inhibiting proteasome. How- ever, its effect on autophagy, which is related with the ubiquitin proteasome pathway （UPP）, remains unclear. Our study aimed to find out its effect on autophagy and possible molecular mechanisms. The results suggested that YSY-0 l A significantly （P〈0.001） inhibited proliferation of PC-3M cells （IC50 was 287 nM for 48 h） in a concentration-dependent and time-dependent manner. YSY-01A （100 nM, 3 h） also induced autophagy in PC-3M ceils through increasing the expression of P53 （P〈0.001）, Beclin-1 （P〈0.001） and LC3 （P〈0.001）, and decreasing the expression of p-roTOR （P〈0.001） as compared with the negative control group. Autophagy stayed at a final stage in PC-3M cells after treated with YSY-01A （400 nM） for 12 h. Meanwhile inhibition of autophagy with chloroquine increased the sensitivity to YSY-01A in PC-3M cells. In conclusion, YSY-01A showed high proliferation inhibitory activity of PC-3M cells and it could induce autophagy in PC-3M cells. Inhibiting autophagy increased the cytotoxic activity of YSY-01A in PC-3M cells. |
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| Keywords: | Proteasome inhibitor YSY-01 A PC-3M Autophagy |
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