Cancer Research Institute, Hangzhou Cancer Hospital, Zhejiang, China.
Life Sciences Research Institute, College of Life and Environmental Sciences, Hangzhou Normal University, Zhejiang, China.
Aging (Albany NY). 2020 Jan 27;12(2):1624-1642. doi: 10.18632/aging.102704.
D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) is the most active water-soluble derivative of vitamin E and has been widely used as a carrier of solvents, plasticizers, emulsifiers, absorbent agents and refractory drug delivery systems. However, its anti-hepatocellular carcinoma (HCC) properties have not been explored. HCC cells were treated with different concentrations of TPGS1000. Cell survival was tested by CCK8 assay, and cell migration was tested by wound healing and Transwell assay. EdU staining verified cell proliferation, and signalling pathway was assayed by Western blot analysis. The BALB/c-nu mouse xenograft model was established to test HCC cell growth . TPGS1000 significantly inhibited the viability and mobility of HCC cells (HepG2, Hep3B and Huh7) in a dose-dependent manner. Cell cycle analysis indicated that TPGS1000 treatment arrested the HCC cell cycle in the G0/G1 phase, and induction of cell apoptosis was confirmed by TUNEL and Annexin V-7-AAD staining. Further pharmacological analysis indicated that collapse of the transmembrane potential of mitochondria, increased ROS generation, PARP-induced cell apoptosis and FoxM1-p21-mediated cell cycle arresting, were involved in the anti-HCC activity of TPGS1000. Moreover, treatment with TPGS1000 effectively impaired the growth of HCC xenografts in nude mice.
D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS1000）是维生素 E 最具活性的水溶性衍生物，已广泛用作溶剂、增塑剂、乳化剂、吸收剂和难溶性药物传递系统的载体。然而，其抗肝癌（HCC）的特性尚未被探索。用不同浓度的 TPGS1000 处理 HCC 细胞。通过 CCK8 测定法检测细胞存活率，通过划痕愈合和 Transwell 测定法检测细胞迁移。EdU 染色验证细胞增殖，并通过 Western blot 分析测定信号通路。建立 BALB/c-nu 小鼠异种移植模型以测试 HCC 细胞生长。TPGS1000 以剂量依赖性方式显著抑制 HCC 细胞（HepG2、Hep3B 和 Huh7）的活力和迁移能力。细胞周期分析表明，TPGS1000 处理将 HCC 细胞周期阻滞在 G0/G1 期，通过 TUNEL 和 Annexin V-7-AAD 染色证实细胞凋亡诱导。进一步的药理学分析表明，线粒体跨膜电位崩溃、ROS 生成增加、PARP 诱导的细胞凋亡以及 FoxM1-p21 介导的细胞周期阻滞参与了 TPGS1000 的抗 HCC 活性。此外，TPGS1000 处理有效损害了裸鼠 HCC 异种移植的生长。
