Saponins isolated from Schizocapsa plantaginea inhibit human hepatocellular carcinoma cell growth in vivo and in vitro via mitogen-activated protein kinase signaling
Saponins isolated from Schizocapsa plantaginea inhibit human hepatocellular carcinoma cell growth in vivo and in vitro via mitogen-activated protein kinase signaling
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从 Schizocapsa plantaginea 中分离的皂苷通过丝裂原激活的蛋白激酶信号抑制体内和体外人肝癌细胞的生长
DOI：
10.1016/s1875-5364(18)30027-x
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发表时间：
2018-01-01
影响因子：
4.6
通讯作者：
Liang Gang
中科院分区：
文献类型：
--
作者：
Sun Yue-Wen;Qiu Han-Chen;Liang Gang
车前草（Schizocapsa plantaginea, Hance）地下藤长期以来被中国少数民族用作抗癌配方的成分。皂苷是该植物地下藤中丰富的次生代谢产物。以人肝癌细胞系SMMC-7721和Bel-7404为实验对象，研究了车前草（Schizocapsa plantaginea, Hance）总皂苷（SSPH）对人肝癌（HCC）的体外治疗作用。流式细胞术检测细胞凋亡和细胞周期阻滞，ELISA检测caspase活化，Western blotting检测PARP、cleaved PARP、丝裂原活化蛋白激酶（MAPK）表达和磷酸化水平。在裸鼠异种移植模型中验证了SSPH的体内抗hcc作用。SSPH对HCC细胞增殖具有明显的抑制作用，且呈时间和浓度依赖性。此外，SSPH通过caspase依赖性信号传导显著诱导细胞凋亡，并在G(2)/M期阻滞细胞周期。SSPH的这些抗增殖作用与细胞外信号调节激酶1/2 （Erk1/2）和c-jun- nh2激酶1/2 （JNK1/2）磷酸化上调和p38MAPK磷酸化降低有关。此外，ERK、UO126和JNK、SP600125抑制剂抑制了SSPH的抗增殖作用，提示ERK和JNK是SSPH诱导的抗增殖作用的效应分子。在体内实验中，我们发现SSPH可以抑制裸鼠异种移植瘤的生长，在体外也具有类似的机制。我们的研究证实了SSPH对人肝癌细胞在体内和体外均有拮抗作用。SSPH作用的分子机制可能与MAPK信号通路密切相关。这些结果表明SSPH对HCC有潜在的治疗作用。
The underground cane of Schizocapsa plantaginea (Hance) has long been used by Chinese ethnic minority as a constituent of anti-cancer formulae. Saponins are abundant secondary metabolic products located in the underground cane of this plant. The potential therapeutic effects of total saponins isolated from Schizocapsa plantaginea (Hance) (SSPH) on human hepatocellular carcinoma (HCC) were tested in vitro in human liver cancer cell lines, SMMC-7721 and Bel-7404. Apoptosis and cell cycle arrest were determined using flow cytometry, caspase activation was determined by ELISA, and PARP, cleaved PARP, mitogen-activated protein kinase (MAPK) expression and phosphorylation were measured using Western blotting analysis. In vivo anti-HCC effects of SSPH were verified in nude mouse xenograft model. SSPH exerted markedly inhibitory effect on HCC cell proliferation in time-and concentration-dependent manner. Moreover, SSPH significantly induced apoptosis through caspase-dependent signaling and arrested cell cycle at G(2)/M phase. These anti-proliferation effects of SSPH were associated with up-regulated phosphorylation of extracellular signal-regulated kinase-1/2 (Erk1/2) and c-jun-NH2-kinase-1/2 (JNK1/2) and reduced phosphorylation of p38MAPK. Furthermore, inhibitors of ERK, UO126, and JNK, SP600125 inhibited the anti-proliferation effects by SSPH, suggesting that Erk and JNK were the effector molecules in SSPH induced anti-proliferative action. During in vivo experiments, SSPH was found to inhibit xenograft tumor growth in nude mice, with a similar mechanism in vitro. Our study confirmed that SSPH exerted antagonistic effects on human liver cancer cells both in vitro and in vivo. Molecular mechanisms underlying SSPH action might be closely associated with MAPK signaling pathways. These results indicated that SSPH has potential therapeutic effects on HCC.