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.

肉苁蓉是一种中草药，具有多种生物学功能。先前的研究已经证明，肉苁蓉苯乙醇苷（CTPG）对多种肿瘤细胞具有抗肿瘤作用。然而，CTPG 对 HepG2 和 BEL-7404 肝细胞癌 (HCC) 细胞的抗肿瘤作用仍然难以捉摸。我们的研究表明，CTPG 通过诱导细胞周期停滞和凋亡显着抑制 HepG2 和 BEL-7404 细胞的生长，这与以 p38、JNK 和 ERK1 磷酸化上调为特征的 MAPK 通路的激活有关。 2和以线粒体膜电位降低为特征的线粒体依赖性通路。细胞色素c的释放随后通过 CTPG 处理增加了 caspase-3、-7、-9 和 PARP 的裂解。此外，CTPG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着抑制HepG2的迁移。有趣的是，CTPG不仅增强了脾细胞的增殖，而且减少了顺铂诱导的脾细胞的凋亡。在H22肿瘤小鼠模型中，CTPG联合顺铂进一步抑制了H22细胞的生长，降低了顺铂的副作用。综上所述，CTPG通过直接抗肿瘤作用和间接免疫增强作用抑制HCC的生长，提高顺铂的抗肿瘤疗效。