Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People's Republic of China.
Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Nanning, 530022, People's Republic of China.
Drug Des Devel Ther. 2021 Dec 1;15:4885-4899. doi: 10.2147/DDDT.S327270. eCollection 2021.
Inhibition of tumor metastasis is a useful strategy to improve the efficacy of cancer therapy. Ventilagolin, a natural 1, 4-naphthoquinone derivative extracted from Benth, has shown promising antitumor effects in previous studies. However, the effects and underlying mechanisms of Ventilagolin against migration, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) remain unclear. The present study has examined these effects and determined whether the proto-oncogene is involved.
The effects of Ventilagolin on migration, invasion, Pim-1 and EMT-related proteins (eg, E-cadherin, N-cadherin, Vimentin) expression were assessed by scratch wound healing, Transwell, qRT-PCR and Western blot assays, respectively. Pim-1 stably overexpressed HepG2 and SMMC-7721 cells were generated to explore whether Ventilagolin inhibited migration, invasion and EMT of HCC cells via regulating Pim-1. Subcutaneous xenograft tumor model in nude mice was established. Histopathological changes of tumor tissues were examined by H&E staining and expressions of Pim-1 and EMT-related proteins were detected by immunohistochemistry.
Ventilagolin significantly ( < 0.01) reduced the expression of Pim-1 levels in HepG2 and SMMC-7721 cells. Compared with the control group, the migration and invasion abilities of Pim-1-overexpressing HepG2 and SMMC-7721 cells were significantly ( < 0.05, < 0.01) enhanced, the expression of E-cadherin was decreased ( < 0.01), and the levels of N-cadherin and Vimentin were upregulated ( < 0.05, < 0.01). Ventilagolin treatment effectively reversed these effects of Pim-1 overexpression. In vivo experiments showed that Ventilagolin could effectively suppress HCC tumor growth, downregulate Pim-1, N-cadherin and Vimentin expression, and upregulate E-cadherin expression.
Ventilagolin suppresses HCC cell proliferation, migration and invasion and reverses EMT process by downregulating Pim-1, suggesting Ventilagolin is a potential therapeutic agent for treatment of HCC.
抑制肿瘤转移是提高癌症治疗效果的一种有效策略。Ventilagolin 是一种从 Benth 中提取的天然 1,4-萘醌衍生物，在之前的研究中显示出了有希望的抗肿瘤作用。然而，Ventilagolin 对肝细胞癌（HCC）迁移、侵袭和上皮-间充质转化（EMT）的作用及其潜在机制尚不清楚。本研究检测了这些作用，并确定原癌基因 是否参与其中。
通过划痕愈合试验、Transwell 试验、qRT-PCR 和 Western blot 试验分别评估 Ventilagolin 对迁移、侵袭、Pim-1 和 EMT 相关蛋白（如 E-钙黏蛋白、N-钙黏蛋白、波形蛋白）表达的影响。生成 Pim-1 稳定过表达的 HepG2 和 SMMC-7721 细胞，以探讨 Ventilagolin 是否通过调节 Pim-1 抑制 HCC 细胞的迁移、侵袭和 EMT。建立裸鼠皮下移植瘤模型。通过 H&E 染色观察肿瘤组织的组织学变化，通过免疫组化检测 Pim-1 和 EMT 相关蛋白的表达。
Ventilagolin 显著（ < 0.01）降低了 HepG2 和 SMMC-7721 细胞中 Pim-1 水平的表达。与对照组相比，Pim-1 过表达的 HepG2 和 SMMC-7721 细胞的迁移和侵袭能力显著增强（ < 0.05， < 0.01），E-钙黏蛋白的表达下调（ < 0.01），N-钙黏蛋白和波形蛋白的水平上调（ < 0.05， < 0.01）。Ventilagolin 处理有效逆转了 Pim-1 过表达的这些作用。体内实验表明，Ventilagolin 能有效抑制 HCC 肿瘤生长，下调 Pim-1、N-钙黏蛋白和波形蛋白的表达，上调 E-钙黏蛋白的表达。
Ventilagolin 通过下调 Pim-1 抑制 HCC 细胞增殖、迁移和侵袭，并逆转 EMT 过程，表明 Ventilagolin 是治疗 HCC 的一种潜在治疗剂。
