title: Sorafenib sensitizes hepatocellular carcinoma cell to cisplatin via suppression of Wnt/β-catenin signaling.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In this study, we found that nuclear accumulation of β-catenin was higher in cisplatin-resistant Huh7 cells than in Huh7 cells, indicating that Wnt signaling was activated in cisplatin-resistant cells. Wnt signaling inhibition increased cisplatin-induced growth inhibition in hepatoma cell. We further demonstrated that sorafenib could inhibit Wnt signaling in Huh7 cells and cisplatin-resistant Huh7 cells. Co-treatment with cisplatin and sorafenib was more effective in inhibiting cancer cell proliferation than cisplatin alone in vitro and in vivo, whereas Wnt3a (Wnt activator) treatment abrogated sorafenib-induced growth inhibition. These data demonstrated that sorafenib sensitizes human HCC cell to cisplatin via suppression of Wnt/β-catenin signaling, thus offering a new target for chemotherapy of HCC.
authors.affiliation: The Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Yongpeng
authors.initials: Y
authors.lastname: Wei
authors.forename: Ningjia
authors.initials: N
authors.lastname: Shen
authors.forename: Zhouchong
authors.initials: Z
authors.lastname: Wang
authors.forename: Guangshun
authors.initials: G
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.forename: Yinghe
authors.initials: Y
authors.lastname: Qiu
authors.forename: Junhua
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib; D060449:Wnt Signaling Pathway / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D002945:Cisplatin