sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway

• 作者: Fang-hai Han Jian-xing Chen Jie Liu Jing Lu Jun-jian Wang Pan-xia Wang Pei-qing Liu Wei Li Ying Guo Yue-huai Hu
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2020,（9）
• 所属期刊栏目: Cardiovascular Pharmacology
• 页码范围: 1150-1157
• 页数: 8页
• 语种: 英文

摘要

Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers,including both hematological and solid tumors.However,the serious cardiotoxic effect restricted its clinical application.We previously have illuminated the protective role of canonical Wnt/β-catenin signaling in Dox-induced cardiotoxicity.Secreted frizzled-related protein 1 (sFRP1) is one of the endogenous inhibitors of both canonical and noncanonical Wnt signaling.In this study,we investigated the relationship between sFRP1 and noncanonical Wnt/PCP-JNK (Wnt/planar cell polarity-c-Jun N-terminal kinase) pathway in Dox-induced cardiotoxicity in vitro and in vivo.We showed that treatment of H9c2 cardiac myoblasts with Dox (1 μJM) time-dependently suppressed cell viability accompanied by significantly decreased sFRP1 protein level and increased Wnt/PCP-JNK signaling.Pretreatment with SP600125,the Wnt/PCP-JNK signaling inhibitor,attenuated Dox-induced apoptosis of H9c2 cells.Overexpression of sFRP1 protected H9c2 cells from Dox-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.After intraperitoneal injection of a cumulative dose of 15 mg/kg Dox,rats displayed significant cardiac dysfunction;their heart showed inhibited Wnt/β-catenin signaling and activated Wnt/PCP-JNK signaling.These results suggest that sFRP1 may be a novel target for Dox-induced cardiotoxicity.