Sorafenib sensitizes hepatocellular carcinoma cell to cisplatin via suppression of Wnt/beta-catenin signaling

作者：Wei Yongpeng; Shen Ningjia; Wang Zhouchong; Yang Guangshun; Yi Bin; Yang Ning; Qiu Yinghe; Lu Junhua^*

来源：Molecular and Cellular Biochemistry, 2013, 381(1-2): 139-144.

DOI：10.1007/s11010-013-1695-6

• Hepatocellular carcinoma
• Cisplatin
• Sorafenib
• Chemoresistance
• Wnt/beta-catenin

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 beta-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/beta-catenin signaling, thus offering a new target for chemotherapy of HCC.

• 出版日期2013-9
• 单位中国人民解放军第二军医大学