期刊
JOURNAL OF CANCER
卷 9, 期 21, 页码 3962-3970出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.25909
关键词
YAP; chemotherapeutic sensitivity; oxaliplatin; Huaier; synergistic effect; Hepatocellular carcinoma
类别
资金
- Natural science foundation of China [81472124, 81774291]
- Talent introduction project of Shanghai Municipal Hospital of Traditional Chinese Medicine [20160501]
- Chen Guang project by Shanghai Municipal Education Commission
- Shanghai Education Development Foundation [17CG43]
- Innovation project of Shanghai University of Traditional Chinese Medicine [JXDXSCXJH10, JXDXSCXJH15]
- Shanghai Sailing Program [18YF1421800]
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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