Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 201100, PR China.
Department of gastroenterology, The First Affiliated Hospital of Nanchang university, Jiangxi, 330006, PR China.
J Ethnopharmacol. 2020 Apr 6;251:112529. doi: 10.1016/j.jep.2019.112529. Epub 2019 Dec 28.
Many studies have confirmed that traditional Chinese herbs exert potential anti-tumor effects. Actinidia Chinensis Planch root has been used as a traditional Chinese medicine (TCM) for thousands of years. However, the mechanism of anti-tumor effects of Actinidia Chinensis Planch root has not been clearly clarified.
To explore the molecular biological mechanisms underlying the inhibitory effect of Actinidia Chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC).
In our previous study, we used mRNA chip analyses to identify genes regulated by acRoots. Further analyses of altered genes led to the identification of a key regulator of genes that responds to acRoots. We explored the effects of acRoots on the proliferation and invasion of HCC cells via cell counting as well as transwell assays, and further explored the molecular mechanisms underlying the effects of acRoots on HCC cells using qRT-PCR, western blot, and Chip-PCR.
Increasing the concentration of acRoots as well as prolonging its action time enhanced the inhibitory activity of acRoots as well as its cytotoxicity against HCC cells. High TARBP2 expression in HCC cells, which is associated with advanced-stage HCC and poor prognoses in HCC patients, was downregulated by treatment with acRoots. Furthermore, acRoots inhibited proliferation, invasion, and epithelial-to-mesenchymal transition by downregulating TARBP2 expression. HCC cells with higher TARBP2 expression were more sensitive to acRoots. The expression of TARBP2 and DLX2 in HCC patients and HCC cell lines was significantly positively correlated, and DLX2 as a transcription factor may promote TARBP2 expression, thereby further activating the JNK/AKT signaling pathway leading to the inhibition of HCC.
acRoots inhibited the malignant behavior of HCC cells by inhibiting TARBP2 expression, which is affected by the transcription factor DLX2, leading to a reduction in JNK/AKT signaling pathway activation.
许多研究证实，传统中药具有潜在的抗肿瘤作用。猕猴桃根已被用作传统中药（TCM）几千年。然而，猕猴桃根的抗肿瘤作用机制尚未得到明确阐明。
探讨猕猴桃根提取物（acRoots）抑制肝癌（HCC）的分子生物学机制。
在我们之前的研究中，我们使用 mRNA 芯片分析来鉴定受 acRoots 调节的基因。对改变的基因进行进一步分析，确定了对 acRoots 反应的基因的关键调节剂。我们通过细胞计数和 Transwell 测定法研究 acRoots 对 HCC 细胞增殖和侵袭的影响，进一步通过 qRT-PCR、western blot 和 Chip-PCR 研究 acRoots 对 HCC 细胞的作用的分子机制。
增加 acRoots 的浓度并延长其作用时间增强了 acRoots 的抑制活性及其对 HCC 细胞的细胞毒性。TARBP2 在 HCC 细胞中的高表达与 HCC 患者的晚期 HCC 和不良预后相关，用 acRoots 处理后其表达下调。此外，acRoots 通过下调 TARBP2 表达抑制增殖、侵袭和上皮间质转化。具有较高 TARBP2 表达的 HCC 细胞对 acRoots 更敏感。TARBP2 和 DLX2 在 HCC 患者和 HCC 细胞系中的表达呈显著正相关，作为转录因子的 DLX2 可能促进 TARBP2 的表达，从而进一步激活 JNK/AKT 信号通路，从而抑制 HCC。
acRoots 通过抑制 TARBP2 表达抑制 HCC 细胞的恶性行为，受转录因子 DLX2 的影响，从而减少 JNK/AKT 信号通路的激活。
