Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells  

作　　者：Xiao-Jing Yan Peng Xie Xu-Fang Dai Ling-Xi Chen Liang-Bo Sun Tao Li Wen-Hui He Zhi-Zhen Xu Gang Huang Feng-Tian He Ji-Qin Lian 

机构地区：[1]Department of Biochemistry and Molecular Biology,Army Medical University,Chongqing 400038,China [2]Department of Educational Science College,Chongqing Normal University,Chongqing 400038,China

出　　处：《Cancer Drug Resistance》2020年第4期947-958,共12页癌症耐药（英文）

基　　金：This study was supported by the National Natural Science Foundation of China(81572375 and 81872024);the Chongqing Natural Science Foundation(cstc2018jcyjA2018).

摘　　要：Aim:Liver cancer is one of the most common malignancies and has a high recurrence rate.However,current treatment strategies do not achieve satisfactory outcomes in the clinic.To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer,we investigated whether dichloroacetate(DCA)could enhance the sensitivity of liver cancer cells to pirarubicin(THP).Methods:Liver cancer cells were treated with DCA alone,THP alone,or DCA and THP combined.Cell viability was determined by the CCK-8 assay.Cell apoptosis was analyzed by flow cytometer.Reactive oxygen species(ROS)were detected using a CM-H2DCFDA fluorescence probe.Protein levels were identified by immunoblotting.Results:The results revealed that DCA significantly enhanced the antitumor effect of THP in liver cancer cells.Changes in morphology and adherence ability were observed,as well as decreased cell viability.The results of flow cytometry showed that the combination of THP and DCA significantly increased apoptosis of liver cancer cells.Moreover,compared with THP alone,combination treatment with DCA significantly increased THP-triggered ROS generation in liver cancer cells.The antioxidant N-acetyl-L-cysteine reversed the synergistic effect of DCA and THP on ROS generation,cell viability and apoptosis.Furthermore,phosphorylation of c-Jun N-terminal kinase(JNK)was significantly increased in the DCA and THP combination group.The effects of DCA and THP on cell viability and apoptosis were inhibited by the JNK inhibitor SP600125.Conclusion:The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the ROS-JNK signaling pathway.

关 键 词：DICHLOROACETATE c-Jun N-terminal kinase liver cancer cells PIRARUBICIN reactive oxygen species 

分 类 号：R73[医药卫生—肿瘤]