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Journal of Cellular Biochemistry

Reversal of Multidrug Resistance in Gastric Cancer Cells by E2F-1 Downregulation In Vitro and In Vivo

Authors

  • Lin-Hai Yan,

    1. Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
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  • Xiao-Tong Wang,

    1. Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
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  • Jie Yang,

    1. Department of Surgery, Rui Kang Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China
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  • Fan-Biao Kong,

    1. Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
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  • Chao Lian,

    1. Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
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  • Wei-Yuan Wei,

    1. Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
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  • Wen Luo,

    1. Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
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  • Yu-Bo Xie,

    Corresponding author
    1. Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
    • Correspondence to: Qiang Xiao and Yu-Bo Xie, Departments of Surgery and Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

      E-mail: xiaoqiang20050@aliyun.com (Q. Xiao), xieyubo715001@aliyun.com (Y.B. Xie)

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  • Qiang Xiao

    Corresponding author
    1. Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
    • Correspondence to: Qiang Xiao and Yu-Bo Xie, Departments of Surgery and Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

      E-mail: xiaoqiang20050@aliyun.com (Q. Xiao), xieyubo715001@aliyun.com (Y.B. Xie)

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ABSTRACT

Transcription Factor E2F-1 plays a critical role in cell cycle regulation and other biological processes in cells. However whether or not it is involved in the multi-drug resistance (MDR) process of gastric cancer has not been fully elucidated yet. To explore the role of E2F-1 in the MDR process of gastric cancer in vitro and in vivo, a cisplatin-resistant gastric cancer cell line with stable downregulation of E2F-1 was established. E2F-1 shRNA led to downregulation of endogenous E2F-1 mRNA and protein. It significantly promoted the sensitivity of SGC7901/DDP cells to cisplatin, doxorubicin, and fluorouracil. Flow cytometry confirmed that the percentage of apoptotic cells increased after E2F-1 downregulation. This notion was further supported by the observation that downregulation of E2F-1 blocked entry into the S-phase of the cell cycle. Furthermore, downregulation of E2F-1 significantly increased intracellular accumulation of doxorubicin. In addition, we determined the in vivo effects of E2F-1 small interfering RNA (shRNA) on tumor size, and apoptotic cells in tumor tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and hematoxylin and eosin staining. In molecular studies, semiquantitative RT-PCR and western blotting revealed that E2F-1 downregulation could inhibit expression of MDR1, MRP, Bcl-2/Bax, c-Myc, Skp2, Survivin, and Cyclin D1. In conclusion: E2F-1 may be involved in regulating multiple signaling pathways in reversing MDR, suggesting that E2F-1 may represent a novel target for gastric cancer therapy. J. Cell. Biochem. 115: 34–41, 2014. © 2013 Wiley Periodicals, Inc.

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