School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Technology of Drug Preparation, Ministry of Education, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, Henan Province, PR China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Technology of Drug Preparation, Ministry of Education, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, Henan Province, PR China.
Eur J Pharmacol. 2017 Nov 15;815:478-486. doi: 10.1016/j.ejphar.2017.08.004. Epub 2017 Aug 9.
Jaridon 6, a novel ent-kaurene diterpenoid derived from Rabdosia rubescens (Hemsl.) Hara, possesses strong anti-tumor activity in esophageal cancer cells. In this study, we explored the underlying molecular events of the anti-tumor activity of Jaridon 6. Cell viability and apoptosis results obtained by flow cytometry confirmed the tumor inhibitory effect of Jaridon 6 in esophageal cancer cells. A cDNA microarray was performed and the observations were validated using quantitative reverse transcription polymerase chain reaction. The microarray data showed that 151 genes were differentially expressed between the untreated group and the Jaridon 6-treated group, among these were 57 upregulated genes, and 94 downregulated genes (P < 0.01, fold change threshold: 2). These included genes such as Wnt, peroxisome, and genes involved in chemokine signaling pathways. In addition, Western blot analysis demonstrated that Jaridon 6 regulated the expression of Wnt pathway proteins, including reduced levels of Dvl 2, survivin and cyclin D1, and increased levels of p-β-catenin, and AXIN2 in EC109 and EC9706 esophageal cancer cells. In addition, recombinant murine Wnt3a could change the regulation of Jaridon 6 on Wnt pathway proteins. Immunohistochemical analysis indicated that the anti-tumor activity of Jaridon 6 was closely related to the Wnt signaling pathway in esophageal cancer cells.
Jaridon 6 是一种新型的 ent-贝壳杉烯二萜类化合物，来源于冬凌草（Hemsl.）Hara，具有很强的抗食管癌活性。在本研究中，我们探讨了 Jaridon 6 抗肿瘤活性的潜在分子事件。通过流式细胞术获得的细胞活力和细胞凋亡结果证实了 Jaridon 6 在食管癌细胞中的肿瘤抑制作用。进行了 cDNA 微阵列分析，并使用定量逆转录聚合酶链反应验证了观察结果。微阵列数据显示，未经处理组和 Jaridon 6 处理组之间有 151 个基因表达存在差异，其中有 57 个上调基因和 94 个下调基因（P<0.01，倍数变化阈值：2）。这些基因包括 Wnt、过氧化物酶体和趋化因子信号通路相关基因等。此外，Western blot 分析表明，Jaridon 6 调节 Wnt 通路蛋白的表达，包括 Dvl 2、存活素和细胞周期蛋白 D1 水平降低，p-β-catenin 和 AXIN2 水平升高，在 EC109 和 EC9706 食管癌细胞中。此外，重组鼠 Wnt3a 可以改变 Jaridon 6 对 Wnt 通路蛋白的调节。免疫组织化学分析表明，Jaridon 6 的抗肿瘤活性与食管癌细胞中的 Wnt 信号通路密切相关。
