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狭叶重楼甾体皂苷类化学成分PSⅡ体外抗肿瘤作用的观察

肖雪, 杨媚, 白鹏, 陈新莲, 刘珊玲, 邹娟, 王和

肖雪, 杨媚, 白鹏, 等. 狭叶重楼甾体皂苷类化学成分PSⅡ体外抗肿瘤作用的观察[J]. 四川大学学报（医学版）, 2012, 43(5): 651-656.
引用本文: 肖雪, 杨媚, 白鹏, 等. 狭叶重楼甾体皂苷类化学成分PSⅡ体外抗肿瘤作用的观察[J]. 四川大学学报（医学版）, 2012, 43(5): 651-656.
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XIAO Xue, YANG Mei, BAI Peng, et al. Observation on Anticancer Function of PSⅡ Isolated from Rhizoma Paridis[J]. Journal of Sichuan University (Medical Sciences), 2012, 43(5): 651-656.
Citation: XIAO Xue, YANG Mei, BAI Peng, et al. Observation on Anticancer Function of PSⅡ Isolated from Rhizoma Paridis[J]. Journal of Sichuan University (Medical Sciences), 2012, 43(5): 651-656.
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栏目: 论著

狭叶重楼甾体皂苷类化学成分PSⅡ体外抗肿瘤作用的观察

  • 1. 四川大学华西第二医院 妇产科 (成都 610041);

  • 2. 四川大学华西基础医学与法医学院 法医物证学教研室 (成都 610041);

  • 3. 四川大学华西第二医院 遗传实验室 (成都 610041);

  • 4. 四川大学华西第二医院 病理科 (成都 610041)

基金项目: 

国家自然科学基金（No.81001159）资助

Observation on Anticancer Function of PSⅡ Isolated from Rhizoma Paridis

  • 1. Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu 610041, China;

  • 2. Department of Forensic Sciences, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China;

  • 3. Lab of Genetics, West China Second Hospital, Sichuan University, Chengdu 610041, China;

  • 4. Department of Pathology, West China Second Hospital, Sichuan University, Chengdu 610041, China

摘要

    摘要
  • 摘要: 目的 研究狭叶重楼甾体皂苷类化学成分（PSⅡ）的抗瘤活性及机制。 方法 分离纯化狭叶重楼主要化合物PSⅡ，根据理化性质、波谱数据鉴定其结构。体外实验中采用MTT法评价PSⅡ对肿瘤细胞株SKOV3的毒性及时效和量效关系，并以化疗药物依托泊苷（VP16）为对照；通过流式技术和缺口末端标记（TUNEL）技术探讨PSⅡ对SKOV3细胞凋亡的影响。采用免疫印迹技术探讨药物对丝裂原激活蛋白酶（MAPKs）和线粒体信号通路的影响。 结果 PSⅡ对SKOV3细胞株的50%生长抑制浓度（IC50）为4.81 μmol/L。流式细胞和TUNEL技术进一步证实了SKOV3细胞经PSⅡ干预后凋亡率增加，并有剂量和时间依赖性（P<0.05）。PSⅡ抑制细胞外信号调节蛋白激酶（ERK）1/2的活性并促进凋亡蛋白Bid、Bax表达增加，下游蛋白procaspase-3以及procaspase-9的表达下调。 结论 PSⅡ通过影响MAPKs信号传导途径靶蛋白，特别是对启始因子ERK1/2活性的抑制，激活线粒体凋亡通路，促进肿瘤细胞的凋亡。

     

    Abstract: Objective To isolate compound Paris saponin Ⅱ(PSⅡ) from Rhizoma Paridis and observe its antitumor activity. Methods PSⅡ was isolated and determined by electrospray ionization-mass spectrometry,1H and 13C nuclear magnetic resonance spectral analysis. PSⅡ was used to treat cancer cells to analyze the toxicity and relative time-and dose-dependent manner. Apoptosis of cells were investigated by flow cytometry and TUNEL assay. Western blotting was used to analyze the effects of PSⅡ to MAPKs and mitochondrial apoptotic pathway. Results The anti-tumor activities of PSⅡ on ovarian carcinoma cell line SKOV3 were investigated. The IC50 of PSⅡ to SKOV3 was 4.81 μmol/L. Increased apoptosis rate in a dose-and time-dependent manner was observed by Flow cytometry and TUNEL. The activity of ERK1/2 was inhibited by PSⅡ and increased expression of cytochrone c, caspase-3 and caspase-9 was also noticed after the treatment of PSⅡ. Conclusion PSⅡ can inhibit the growth of ovarian cancer cells SKOV3 through affecting the key proteins on MAPKs pathway and inhibiting the activity of ERK1/2 and eventually eliciting programmed cell death of SKOV3. The mitochondrial apoptotic pathway may be involved in the PSⅡ induced apoptosis.

     

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    • 参考文献(14)
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出版历程
  • 收稿日期:  2012-04-10
  • 修回日期:  2012-06-17
  • 发布日期:  2012-09-19

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