China Oncology ›› 2021, Vol. 31 ›› Issue (4): 263-267.doi: 10.19401/j.cnki.1007-3639.2021.04.004

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NDRG2 increases bladder cancer cell sensitivity to cisplatin by inhibiting Bcl-2 expression

LI Ruixiao 1 , TANG Qisheng 1 , MA Shanjin 1 , ZHANG Bo 1 , LI Xuelian 2 , ZHANG Zhiming   

  1. 1. Department of Urology, Tangdu Hospital, the Air Force Medical University, Xi'an 710038, Shaanxi Province, China; 2. Department of Surgery, Xi'an Hospital of Traditional Chinese Medicine, Xi'an 710002, Shaanxi Province, China
  • Online:2021-04-30 Published:2021-04-29
  • Contact: ZHANG Zhiming E-mail:

Abstract: Background and purpose: N-Myc down stream-regulated gene 2 (NDRG2) is a new type of tumor suppressor gene, which plays an important role in cell proliferation and apoptosis. The chemotherapy resistance of bladder cancer is the main cause for the failure of clinical treatment; therefore, this study aimed to clarify the expression of NDRG2 and its potential role in the pathogenesis of cisplatin (CDDP) resistance in bladder cancer cells. Methods: Bladder cancer T24 cells were continuously passaged by increasing the CDDP concentration for 6 months to obtain CDDP-resistant T24/CR cell lines. Lentiviral transfection was used to achieve high expression of NDRG2 in T24/CR. Cell viability was measured by MTT, apoptosis and transwell invasion assay were performed. The effect of NDRG2 overexpression on T24 cell resistance to CDDP was compared. Bcl-2-siRNA transient transfection was used to knock down the expression of NDRG2 in T24 cells, and then the expression in different groups was detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression level of NDRG2 mRNA. Results: The expression level of NDRG2 was significantly down-regulated in CDDP-resistant bladder cancer cells. Exogenous overexpression of NDRG2 enhanced the sensitivity to CDDP and inhibited the viability and invasion of bladder cancer cells in the presence of CDDP. Knockdown of NDRG2 expression had no significant effect on the expression of Bcl-2. Knockdown of Bcl-2 could effectively eliminate the effect of low NDRG2 expression on the viability and apoptosis of bladder cancer cells, and could restore the sensitivity to CDDP in bladder cancer cells. Conclusion: The unbalance of NDRG2/Bcl-2 maybe the key mechanism of CDDP resistance in advanced bladder cancer. Enhanced expression of NDRG2 might be used as a candidate for the treatment of CDDP-resistant or refractory bladder cancer.

Key words: Cisplatin, N-Myc down steam-regulated gene 2, Resistance, Bcl-2