重楼皂苷G通过CIP2A/PP2A信号通路抑制淋巴瘤细胞生长并促进凋亡及自噬的机制研究  

Polyphyllin G inhibits growth and promotes apoptosis of lymphoma cells through CIP2A/Akt signaling pathway

作　　者：刘雪文 向雨晨 刘洋洋 司渊 刘莹 郭阳[1,2,3,4] LIU Xue-wen;XIANG Yu-chen;LIU Yang-yang;SI Yuan;LIU Ying;GUO Yang(School of Basic Medical Sciences;Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry;Hubei Key Laboratory of Embryonic Stem Cell Research;Biomedical Research Institute,Hubei University of Medicine,Shiyan 442000,China)

机构地区：[1]湖北医药学院基础医学院 [2]湖北医药学院武当特色中药研究湖北省重点实验室 [3]湖北医药学院胚胎干细胞湖北省重点实验室 [4]湖北医药学院生物医药研究院,十堰442000

出　　处：《天然产物研究与开发》2020年第10期1767-1772,共6页Natural Product Research and Development

基　　金：国家自然科学基金青年项目(81702930);湖北医药学院研究生启动金(2019QDJZR16);武当特色中药研究湖北省重点实验室开放课题(WDCM2019008);胚胎干细胞湖北省重点实验室开放课题(2020ESOF007)。

摘　　要：为探究一种从延龄草(Trillium tschonoskii Maxim)中提取的活性化合物polyphyllin G(PPG)在人淋巴瘤细胞中的抑制作用及机制,采用CCK-8和细胞计数测定法检测增殖抑制作用,通过流式细胞术和蛋白印迹检测细胞凋亡、自噬及上游机制。结果显示,PPG在Raji淋巴瘤细胞系中抑制生长并促进凋亡及自噬。PPG显著下调蛋白磷酸酶2A的癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)的表达。PPG增加了CIP2A下游分子蛋白磷酸酶2A(protein phosphatase 2A,PP2A)的活性,并进而降低了Akt的磷酸化。进一步,PP2A抑制剂冈田酸能够拮抗PPG对细胞增殖的抑制作用及对凋亡、自噬的诱导作用,表明PP2A是PPG通过下调CIP2A诱导细胞凋亡及自噬的关键环节。总之,以上结果表明,PPG可能通过抑制CIP2A/PP2A/Akt信号通路抑制淋巴瘤细胞生长并促进凋亡及自噬。PPG有望成为治疗淋巴瘤的潜在抗癌药物。To investigate the effect and possible mechanisms of polyphyllin G(PPG),a bioactive compound extracted from the Trillium tschonoskii Maxim,on human lymphoma cells,the present study used CCK-8 and cell counting assays to detect the proliferation inhibition.Flow cytometric and western blot assays were performed to assess apoptosis,autophagy and investigate the mechanism.The results indicated that PPG inhibited growth,promoted apoptosis and autophagy in Raji lymphoma cells.PPG significantly down-regulated the expression of cancerous inhibitor of protein phosphatase 2A(CIP2A).PPG increased the activity of protein phosphatase 2A(PP2A),a downstream molecule of CIP2A.And PP2A in turn inhibited the phosphorylation of Akt.Furthermore,the PP2A inhibitor okadaic acid antagonized the effect of PPG on cell proliferation,apoptosis,and autophagy.These results indicated that PP2A played a critical role in PPG induced apoptosis and autophagy by down-regulating CIP2A.Conclusively,the above results showed that PPG suppressed growth and promoted the apoptosis and autophagy of lymphoma cells via inhibiting CIP2A/PP2A/Akt signaling pathways.PPG is a potential anticancer drug for the treatment of lymphoma.

关 键 词：淋巴瘤 polyphyllin G CIP2A 凋亡 自噬 

分 类 号：R966[医药卫生—药理学]