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World J Gastroenterol. Jul 14, 2013; 19(26): 4155-4165
Published online Jul 14, 2013. doi: 10.3748/wjg.v19.i26.4155
Published online Jul 14, 2013. doi: 10.3748/wjg.v19.i26.4155
Reversal of multidrug resistance in gastric cancer cells by CDX2 downregulation
Lin-Hai Yan, Xiao-Tong Wang, Chao Lian, Fan-Biao Kong, Wei-Yuan Wei, Wen Luo, Qiang Xiao, Departments of Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Jie Yang, Department of Surgery, Rui Kang Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Yu-Bo Xie, Departments of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Xiao Q and Xie YB contributed equally to this work; Xiao Q and Xie YB designed the research; Yan LH performed the research; Wang XT, Yang J, Kong FB, Lian C, Wei WY and Luo W provided the reagents; Yan LH analyzed the data and wrote the paper.
Supported by Grants from the Natural Science Foundation of China, No. 81060201; Natural Science Foundation of Guangxi, No. 2011GXNSFA018273 and No. 2013GXNSFAA019163; and the Key Health Science Foundation of Guangxi, No. 1298003-2-6
Correspondence to: Qiang Xiao, Professor, Department of Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China. xiaoqiang20050@aliyun.com
Telephone: +86-771-5358325 Fax: +86-771-5358325
Received: March 20, 2013
Revised: May 6, 2013
Accepted: June 4, 2013
Published online: July 14, 2013
Revised: May 6, 2013
Accepted: June 4, 2013
Published online: July 14, 2013
Core Tip
Core tip: Modulator of multidrug resistance (MDR) gene is a direct transcriptional target of CDX2. However, we still speculate whether CDX2 affects MDR through other ways. Our results showed that downregulation of CDX2 significantly promoted sensitivity of SGC7901/DDP cells to anticancer drugs, and increased the percentage of apoptotic cells. Downregulation of CDX2 potentiated G1 phase arrest of the cell cycle. Furthermore, it significantly increased intracellular accumulation of doxorubicin. We conclude that downregulation of CDX2 can efficiently reverse MDR via inhibition of apoptosis/cell-cycle-related gene expression (c-Myc, survivin and cyclin D1).