Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma

• Published in: Biochimica et biophysica acta. General subjects Vol. 1862; no. 4; pp. 1017 - 1030
• Main Authors: Feng, Fan, Jiang, Qiyu, Cao, Shuang, Cao, Yu, Li, Ruisheng, Shen, Lijun, Zhu, Hua, Wang, Tao, Sun, Lijun, Liang, Erguang, Sun, Huiwei, Chai, Yantao, Li, Xiaojuan, Liu, Genyan, Yang, Ruichang, Yang, Zhi, Yang, Yongping, Xin, Shaojie, Li, Bo-an
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2018
• Subjects: Animals; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; drugs; enzyme inhibitors; Gene Expression Regulation, Neoplastic - drug effects; Hep G2 Cells; Hepatocellular carcinoma; hepatoma; Humans; immunohistochemistry; Kaplan-Meier Estimate; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; luciferase; Metabolism and clearance; metastasis; Mice, SCID; Multi-drug resistance; Niacinamide - analogs & derivatives; Niacinamide - metabolism; Niacinamide - therapeutic use; patients; Phenylurea Compounds - metabolism; Phenylurea Compounds - therapeutic use; Pregnane X receptor; prognosis; Protein Kinase Inhibitors - metabolism; Protein Kinase Inhibitors - therapeutic use; quantitative polymerase chain reaction; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; reporter genes; RNA Interference; Sorafenib; Western blotting; Xenograft Model Antitumor Assays - methods; Hepatocellular carcinoma; Multi-drug resistance; Pregnane X receptor; Sorafenib; Metabolism and clearance

Kinase inhibitor sorafenib is the most widely used drug for advanced HCC clinical treatment nowadays. However, sorafenib administration is only effective for a small portion of HCC patients, and the majority develop sorafenib-resistance during treatment. Thus, it is urgent to discover the endogenous...