title: Inhibition of IGFBP-2 improves the sensitivity of bladder cancer cells to cisplatin via upregulating the expression of maspin.
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.
authors.affiliation: Department of Urinary Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Urinary Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yun
authors.affiliation: Department of Urinary Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Urinary Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015843:Serpins / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D018971:Insulin-Like Growth Factor Binding Protein 2; D034741:RNA, Small Interfering; C085344:SERPIN-B5; D015843:Serpins; D002945:Cisplatin