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FSTL1 increases cisplatin sensitivity in epithelial ovarian cancer cells by inhibition of NF-κB pathway

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Abstract

Objective

To investigate the effects of FSTL1-mediated NF-κB signaling pathway on cisplatin (DDP) sensitivity of EOC cells.

Methods

FSTL1 expression was determined in epithelial ovarian cancer (EOC) tissues and corresponding adjacent tissues using immunohistochemistry. SKOV3 and SKOV3/DDP cells were transfected and grouped into Blank, Vector, and FSTL1 groups. The sensitivity and 50% inhibitory concentration (IC50) of cells treated with different concentrations of DDP were detected by MTT assay. SKOV3/DDP cells were treated with 20 μM DDP, followed by evaluation of cell proliferation, cell apoptosis and determination of NF-κB pathway-related proteins while SKOV3 cells without.

Results

FSTL1 expression in EOC tissues and cells was significantly down-regulated, especially decreased in DDP-resistant EOC cells SKOV3/DDP. In SKOV3 cells and SKOV3/DDP cells, the cell viability was reduced and the DDP sensitivity was improved with the decreased IC50 after over-expressing FSTL1. Compared with Blank group, FSTL1 group had declined number of SKOV3 cell colonies and increased cell apoptosis, with obvious up-regulations of FSTL1, Bax/Bcl-2 and cleaved caspase-3 expression and the down-regulations of p-IκBα, p-p65 and survivin expression. Combination of up-regulation of FSTL1 and DDP treatment can also effectively reduce cell colony forming, increase cell apoptosis, and inhibit NF-κB pathway activity of SKOV3/DDP cells. Moreover, this combination can also significantly suppress the growth of subcutaneous xenograft tumors in nude mice.

Conclusion

FSTL1 may inhibit NF-κB signaling pathway to suppress the growth and promote the apoptosis of epithelial ovarian cancer cells, and thereby enhancing its DDP sensitivity.

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Authors and Affiliations

  1. Department of Gynecology, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang, 050011, Hebei, China

    Ya-Kun Liu, Ya-Jing Jia, Shi-Hao Liu & Jing Ma

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Correspondence to Ya-Kun Liu.

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Liu, YK., Jia, YJ., Liu, SH. et al. FSTL1 increases cisplatin sensitivity in epithelial ovarian cancer cells by inhibition of NF-κB pathway. Cancer Chemother Pharmacol 87, 405–414 (2021). https://doi.org/10.1007/s00280-020-04215-9

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