Huaier Augmented the Chemotherapeutic Sensitivity of Oxaliplatin via Downregulation of YAP in Hepatocellular Carcinoma

槐耳通过下调肝细胞癌中的 YAP 增强奥沙利铂的化疗敏感性

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作者:Yuquan Tao, Liang Shan, Xin Xu, Hongyuan Jiang, Rui Chen, Zijun Qian, Zongguo Yang, Bin Liang, Haiyin Zheng, Feng Cai, Yongchun Yu, Lifang Ma

Abstract

For unresectable Hepatocellular carcinoma (HCC), chemotherapy is still an important treatment strategy. Oxaliplatin (Oxa) is an effective treatment of HCC after sorafenib treatment failure. However, the intrinsic or acquired resistance of Oxa affected the chemotherapeutic sensitivity. By analyzing the data of GEO Database, we found that Oxa aberrantly increased the expression of Cysteine-rich61 (Cyr61) in HCC cell lines. Subsequently, in Bel-7404 and SMMC-7721 cells after treated with Oxa, it was verified that the expression of Cyr61 and Yes-associated protein (YAP) was increased. Moreover, we found that blockade of YAP promoted Oxa-induced cell apoptosis for the first time. Meanwhile, our previous study demonstrated that Huaier (HE) inhibited the expression of YAP. Further study found that combination treatment of Oxa and HE had a significantly synergistic anti-cancer effect and significantly inhibited the expression of YAP and apoptosis related proteins. Taken together, we have observed that overexpression of YAP significantly reduced the chemotherapeutic sensitivity of Oxa in HCC for the first time. Combination treatment of Oxa and HE solved this problem.

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