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

Zhu,Haipeng; Yun,Feng; Shi,Xiaoxue; Wang,Dong

doi:10.3892/ijmm.2015.2250

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

Authors:
- Haipeng Zhu
- Feng Yun
- Xiaoxue Shi
- Dong Wang
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Affiliations: Department of Urinary Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: June 17, 2015 https://doi.org/10.3892/ijmm.2015.2250
Pages: 595-601

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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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