Cinobufacini inhibits epithelial-mesenchymal transition of human hepatocellular carcinoma cells through c-Met/ERK signaling pathway
Cinobufacini inhibits epithelial-mesenchymal transition of human hepatocellular carcinoma cells through c-Met/ERK signaling pathway
复制标题
华蟾素通过 c-Met/ERK 信号通路抑制人肝癌细胞的上皮间质转化。
DOI：
10.5582/bst.2018.01082
复制
发表时间：
2018-06-01
影响因子：
5.5
通讯作者：
Wang, Zhixue
中科院分区：
文献类型：
--
作者：
Qi, Fanghua;Wang, Jinjing;Wang, Zhixue
华蟾素是从中华大蟾蜍（Bufo bufo gargarizans Cantor）的皮肤和腮腺毒腺中提取的水提物，是我国著名的传统中药，在临床上广泛应用于癌症的治疗。其治疗效果在肝癌中尤其显著。然而，华蟾素诱导人肝细胞癌（HCC）细胞的确切机制仍不十分清楚。本研究旨在探讨华蟾素对HepG 2细胞侵袭转移的抑制作用及其机制。上皮-间质转化（EMT）被认为是肝癌转移的重要起始步骤。不同浓度华蟾素处理HepG 2细胞后，EMT相关的E-cadherin表达增加，N-cadherin和Vimentin表达减少，EMT相关的转录因子Snail和Twist表达减少。华蟾素可抑制c-Met的磷酸化，并呈剂量依赖性降低c-Met激活的信号转导通路下游激酶MEK 1/2和ERK 1/2的表达。另外，不同浓度华蟾素处理后，HepG 2细胞MMP-2和MMP-9的表达均明显降低。综上所述，本研究提示华蟾素可以通过c-Met/ERK信号通路抑制EMT来阻止HepG 2细胞的迁移和侵袭，这可能为华蟾素治疗肝癌提供实验依据。
Cinobufacini, an aqueous extract from the skins and parotid venom glands of the toad Bufo bufo gargarizans Cantor, is a well known traditional Chinese medicine widely used in clinical cancer therapy in China. Its therapeutic effect is especially pronounced in liver cancer. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. Here, we investigated the effects and mechanisms of cinobufacini on inhibiting HepG2 cells invasion and metastasis. Epithelial-mesenchymal transition (EMT) is identified as an important initiation step for HCC metastasis. After the HepG2 cells were treated with different concentrations of cinobufacini, the expression of EMT related E-cadherin was increased while N-cadherin and Vimentin were decreased, and the expression of EMT related transcription factors Snail and Twist were decreased. Moreover, the phosphorylation of c-Met was inhibited by cinobufacini, and the expression of MEK1/2 and ERK1/2, the downstream kinase of the signal transduction pathway activated by c-Met, also decreased in a dose-dependent manner with cinobufacini. In addition, after the cells were treated with different concentrations of cinobufacini, there was a significant decrease in MMP-2 and MMP-9 expression in HepG2 cells. In conclusion, the current study suggested cinobufacini could prevent HepG2 cells migration and invasion via inhibiting EMT through c-Met/ERK signaling pathway, which might provide experimental evidence for cinobufacini treatment of HCC.