Yang Hong, Li Xiao-dong, Zhou Ying, Ban Xiaojiao, Zeng Ting-ting, Li Lei, Zhang Bao-zhu, Yun Jingping, Xie Dan, Guan Xin-Yuan, Li Yan
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Guangdong Esophageal Cancer Institute, Guangzhou, China.
Oncotarget. 2015 Sep 22;6(28):26079-89. doi: 10.18632/oncotarget.4581.
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients' drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy (P < 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.
食管鳞状细胞癌（ESCC）是东亚国家最致命的消化道恶性肿瘤之一。包括辅助化疗和新辅助化疗在内的多模式疗法已越来越多地用于晚期ESCC患者。然而，化疗效果常常受到患者耐药性的限制。本研究表明，真核翻译起始因子5A2（EIF5A2）过表达诱导ESCC细胞的干性和化疗耐药性。我们发现ESCC细胞中EIF5A2过表达导致对5-氟尿嘧啶（5-FU）、多西他赛和紫杉醇的化疗耐药性增加。相反，抑制eIF5A2的短发夹RNA（shRNAs）增加了肿瘤对这些化疗药物的敏感性。此外，EIF5A2过表达与接受食管切除术后紫杉烷类化疗的ESCC患者较差的总生存率相关（P<0.05）。基于这些结果，我们认为EIF5A2可能是为ESCC患者选择合适化疗方案的预测生物标志物，EIF5A2抑制剂可考虑作为联合治疗以增强ESCC患者的化疗敏感性。
