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  • Inhibition of IGFBP-2 improves the sensitivity of bladder cancer cells to cisplatin via upregulating the expression of maspin.

Inhibition of IGFBP-2 improves the sensitivity of bladder cancer cells to cisplatin via upregulating the expression of maspin.

International journal of molecular medicine (2015-06-18)
Haipeng Zhu, Feng Yun, Xiaoxue Shi, Dong Wang
ABSTRACT

The present study aimed to reveal the association between insulin-like growth factor binding protein-2 (IGFBP-2) and the sensitivity of bladder cancer cells to cisplatin, and determine the underlying mechanism involving maspin. A total of 32 bladder cancer tissue samples were collected for analysis. Cells of the BIU87 human bladder cancer cell line were cultured and a cisplatin-resistant subline (BIU87-CisR) was established by continuous exposure of the cells to cisplatin. Targeted inhibition of IGFBP-2 in the BIU87-CisR cells was performed using small interfering RNA technology. The expression levels of IGFBP-2 and maspin in the tissue samples and cells were analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Cell viability following treatment in each group was evaluated using a Cell Counting Kit-8 assay subsequent to treatment with 3 μM cisplatin. The cell cycle and apoptotic rate of the BIU87-CisR cells were analyzed using flow cytometry. Finally, maspin-overexpressing BIU87-CisR cells were used to confirm the effect of maspin on the sensitivity of the cells to cisplatin. The expression levels of IGFBP-2 in chemoresistant patients and BIU87-CisR cells were significantly increased, compared with those in the chemosensitive patients and BIU87 cells, respectively. However, the expression levels of maspin were lower in the cisplatin-resistant tissue and cells, and was enhanced by IGFBP-2 inhibition. Cisplatin (3 μM) caused marked proliferation inhibition, cell cycle arrest and apoptosis of the BIU87-CisR cells, the effect of which was enhanced by IGFBP-2 silencing. Overexpression of maspin also improved the sensitivity of the BIU87-CisR cells to cisplatin. In conclusion, inhibition of IGFBP-2 improved the sensitivity of bladder cancer cells to cisplatin by elevating the expression of maspin.

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