Inhibition of Eukaryotic Initiating Factor eIF4E Overcomes Abemaciclib Resistance in Gastric Cancer

作     者：Huo-long ZHA Wei CHEN Wei SHI Ying-ying LIAO Huo-long ZHA;Wei CHEN;Wei SHI;Ying-ying LIAO

作者机构：Department of GastroenterologyRenmin HospitalHubei University of MedicineShiyan 442000China Department of Critical Care MedicineTaihe HospitalHubei University of MedicineShiyan 442000China 

出 版 物：《Current Medical Science》 (当代医学科学（英文）)

年 卷 期：2023年第43卷第5期

页      面：927-934页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Nature Science Foundation of Hubei Province(No.2017CFB606) 

主　　题：eIF4E CDK4/6 ribavirin gastric cancer resistance 

摘      要：Objective Aberrant activating mutations in cyclin-dependent kinases 4 and 6(CDK4/6)are common in various cancers,including gastroesophageal *** CDK4/6 inhibitors,such as abemaciclib and palbociclib,have been approved for breast cancer treatment,their effectiveness as a monotherapy remains limited for gastroesophageal *** present study explored the underlying mechanism of abemaciclib *** Abemaciclib-resistant gastric cancer cell lines were generated,and the phospho-eukaryotic translation initiation factor 4E(p-eIF4E)and eIF4E expression was compared between resistant and parental cell *** order to analyze the role of eIF4E in cell resistance,siRNA knockdown was *** effectiveness of ribavirin alone and its combination with abemaciclib was evaluated in the gastric cancer xenograft mouse *** The upregulation of eIF4E was a common feature in gastric cancer cells exposed to prolonged abemaciclib *** cancer cells with increased eIF4E levels exhibited a better response to eIF4E inhibition,especially those that were resistant to ***,which is an approved anti-viral drug,significantly improved the efficacy of abemaciclib,both in vitro and in vivo,by inhibiting ***,ribavirin effectively suppressed the abemaciclib-resistant gastric cancer growth in mice without causing *** These findings suggest that targeting eIF4E can enhance the abemaciclib treatment for gastric cancer,proposing the potential combination therapy of CDK4/6 inhibitors with ribavirin for advanced gastric cancer.