Marsdeniae tenacissima extract-induced growth inhibition and apoptosis in hepatoma carcinoma cells is mediated through the p53/nuclear factor-κB signaling pathway.
Marsdeniae tenacissima extract-induced growth inhibition and apoptosis in hepatoma carcinoma cells is mediated through the p53/nuclear factor-κB signaling pathway.
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Marsdeniae tenacissima 提取物诱导的肝癌细胞生长抑制和凋亡是通过 p53/核因子-kappa B 信号通路介导的
DOI：
10.3892/etm.2017.4833
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发表时间：
2017-09
影响因子：
2.7
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Wang Z;Ying YM;Li KQ;Zhang Y;Chen BY;Zeng JJ;He XJ;Jiang MM;Chen BX;Wang Y;Xu XD;Hao K;Zhu MH;Zhang W
一种传统中药的提取物，马蹄莲（商品名，小爱萍）已经被批准在中国市场上作为癌症化疗药物使用了几十年。先前的研究已经证明了M. tenacissima提取物（MTE）对多种癌细胞的细胞抑制和促凋亡作用。然而，MTE对肝癌细胞增殖和凋亡的作用及其潜在机制尚不清楚。本研究通过增加MTE浓度（0 ~ 320µl/ml）培养Bel-7402细胞，探讨MTE对Bel-7402细胞增殖和凋亡的影响及其可能机制。3-（4,5-二甲基噻唑-2-基）-5（3-羧基甲氧基苯基）-2-（4-磺苯基）- 2h -四氮唑、内盐和碘化丙啶（PI）染色的流式细胞术检测表明，MTE通过将细胞周期阻滞在S期，呈剂量依赖性地抑制Bel-7402细胞的增殖（P<0.05）。Annexin v -异硫氰酸荧光素pi染色流式细胞术证实，MTE在160和240µl/ml时均有显著的促凋亡作用（P<0.001）。逆转录-定量聚合酶链反应和western blot分析显示，MTE（160和240µl/ml）显著下调b细胞淋巴瘤(Bcl)-2 (P<0.01)，上调Bcl-2相关X蛋白（P<0.01）和激活caspase-3 （P<0.05）。此外，160或240µl/ml MTE处理Bel-7402细胞后，小鼠双分钟2 （MDM2）水平显著下调（P<0.001）， p53活性显著升高（P<0.001），核因子(NF)-κB通路受到抑制（P<0.001）。上述结果表明，MTE抑制Bel-7402细胞生长并表现出促凋亡作用，其机制可能是下调mdm2诱导的p53依赖性线粒体凋亡通路，阻断NF-κB通路。总的来说，这些数据初步确定了MTE在肝癌细胞中的重要作用，并表明MTE可能是肝细胞癌治疗的有希望的候选者。
An extract from a traditional Chinese herb, Marsdeniae tenacissima (trade name, Xiao-Ai-Ping) has been approved for use on the Chinese market as a cancer chemotherapeutic agent for decades. Previous studies have demonstrated the cytostatic and pro-apoptotic effects of M. tenacissima extract (MTE) in multiple cancer cells. However, the contributions of MTE to the proliferation and apoptosis of hepatoma carcinoma cells and the underlying mechanisms remain unclear. In the present study, Bel-7402 cells were incubated with increasing concentrations of MTE ranging from 0–320 µl/ml to explore the effects and potential mechanisms of MTE on the proliferation and apoptosis of Bel-7402 cells. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt and propidium iodide (PI)-stained flow cytometry assays demonstrated that MTE significantly suppressed the proliferation of Bel-7402 cells in a dose-dependent manner by arresting the cell cycle at S phase (P<0.05). Annexin V-fluorescein isothiocyanate PI-stained flow cytometry confirmed the significantly pro-apoptotic effect of MTE at both 160 and 240 µl/ml (P<0.001). Reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that MTE (both 160 and 240 µl/ml) induced a significant downregulation of B-cell lymphoma (Bcl)-2 (P<0.01), upregulation of Bcl-2-associated X protein (P<0.01) and activation of caspase-3 (P<0.05). Furthermore, a significant downregulation of murine double minute-2 (MDM2) (P<0.001) and activation of p53 (P<0.001) in Bel-7402 cells following treatment with 160 or 240 µl/ml MTE was observed, accompanied by the inhibition of the nuclear factor (NF)-κB pathway (P<0.001). These results suggested that MTE inhibited growth and exhibited pro-apoptotic effects in Bel-7402 cells, which was mediated by downregulation of the MDM2-induced p53-dependent mitochondrial apoptosis pathway and blocking the NF-κB pathway. Overall, these data serve as preliminary identification of the significant roles of MTE in hepatic carcinoma cells, and suggest that MTE may be a promising candidate for hepatocellular carcinoma therapy.
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影响因子：
9.8
作者：
Altekruse, Sean F.;Henley, S. Jane;Cucinelli, James E.;McGlynn, Katherine A.
通讯作者：
McGlynn, Katherine A.
DOI：
10.1006/bbrc.2000.2786
发表时间：
2000-06-07
影响因子：
3.1
作者：
Ikeda, A;Sun, XG;Yamamoto, K
通讯作者：
Yamamoto, K
影响因子：
0.4
作者：
Huang, T.;Gong, W. H.;Qian, H.
通讯作者：
Qian, H.
影响因子：
--
作者：
Han SY;Ding HR;Zhao W;Teng F;Li PP
通讯作者：
Li PP
影响因子：
20.3
作者：
Gu, LB;Findley, HW;Zhou, MX
通讯作者：
Zhou, MX