Cistanche tubulosa Phenylethanoid Glycosides Induce Apoptosis of Hepatocellular Carcinoma Cells by Mitochondria-Dependent and MAPK Pathways and Enhance Antitumor Effect through Combination with Cisplatin.
Cistanche tubulosa Phenylethanoid Glycosides Induce Apoptosis of Hepatocellular Carcinoma Cells by Mitochondria-Dependent and MAPK Pathways and Enhance Antitumor Effect through Combination with Cisplatin.
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管花肉苁蓉苯乙醇苷通过线粒体依赖性和MAPK途径诱导肝癌细胞凋亡，并与顺铂联合增强抗肿瘤作用
DOI：
10.1177/15347354211013085
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发表时间：
2021-01
影响因子：
2.9
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Yuan P;Fu C;Yang Y;Adila A;Zhou F;Wei X;Wang W;Lv J;Li Y;Xia L;Li J
管花肉桂是一种中草药，具有多种生物学功能。以往的研究已经证明，肉桂苯乙醇苷(CTPG)对多种肿瘤细胞具有抗肿瘤作用。然而，CTPG对肝癌细胞株HepG2和BEL-7404的抗肿瘤作用尚不清楚。我们的研究表明，CTPG通过诱导细胞周期停滞和凋亡而显著抑制HepG2和BEL-7404细胞的生长，这与激活以p38、JNK和ERK1/2上调为特征的MAPK通路和以线粒体膜电位降低为特征的线粒体依赖通路有关。细胞色素c的释放以及caspase-3、-7、-9和PARP的裂解随后被CTPG处理增加。此外，CTPG还通过降低基质金属蛋白酶-2和血管内皮生长因子的水平，显著抑制HepG2细胞的迁移。有趣的是，CTPG不仅促进了脾细胞的增殖，而且还减少了顺铂诱导的脾细胞的凋亡。在H22荷瘤小鼠模型中，CTPG联合顺铂进一步抑制H22细胞的生长，减少顺铂的副作用。综上所述，CTPG通过直接抗肿瘤作用和间接免疫促进作用抑制肝癌生长，提高顺铂的抗肿瘤作用。
Cistanche tubulosa is a type of Chinese herbal medicine and exerts various biological functions. Previous studies have been demonstrated that Cistanche tubulosa phenylethanoid glycosides (CTPG) exhibit antitumor effects on a variety of tumor cells. However, the antitumor effects of CTPG on HepG2 and BEL-7404 hepatocellular carcinoma (HCC) cells are still elusive. Our study showed that CTPG significantly inhibited the growth of HepG2 and BEL-7404 cells through the induction of cell cycle arrest and apoptosis, which was associated with the activation of MAPK pathways characterized by the up-regulated phosphorylation of p38, JNK, and ERK1/2 and mitochondria-dependent pathway characterized by the reduction of mitochondrial membrane potential. The release of cytochrome c and the cleavage of caspase-3, -7, -9, and PARP were subsequently increased by CTPG treatment. Moreover, CTPG significantly suppressed the migration of HepG2 through reducing the levels of matrix metalloproteinase-2 and vascular endothelial growth factor. Interestingly, CTPG not only enhanced the proliferation of splenocytes but also reduced the apoptosis of splenocytes induced by cisplatin. In H22 tumor mouse model, CTPG combined with cisplatin further inhibited the growth of H22 cells and reduced the side effects of cisplatin. Taken together, CTPG inhibited the growth of HCC through direct antitumor effect and indirect immunoenhancement effect, and improved the antitumor efficacy of cisplatin.