Department of Gynecology, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang, 050011, Hebei, China.
Cancer Chemother Pharmacol. 2021 Mar;87(3):405-414. doi: 10.1007/s00280-020-04215-9. Epub 2021 Jan 3.
To investigate the effects of FSTL1-mediated NF-κB signaling pathway on cisplatin (DDP) sensitivity of EOC cells.
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.
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.
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.
探讨 FSTL1 介导的 NF-κB 信号通路对顺铂（DDP）敏感性的影响。
采用免疫组织化学法检测上皮性卵巢癌（EOC）组织及相应癌旁组织中 FSTL1 的表达。转染 SKOV3 和 SKOV3/DDP 细胞，分为空白组、载体组和 FSTL1 组。采用 MTT 法检测不同浓度 DDP 处理细胞的敏感性和半数抑制浓度（IC50）。用 20 μM DDP 处理 SKOV3/DDP 细胞，评估细胞增殖、细胞凋亡情况，并测定 NF-κB 通路相关蛋白。而 SKOV3 细胞不做处理。
EOC 组织和细胞中 FSTL1 的表达明显下调，尤其是在 DDP 耐药的 EOC 细胞 SKOV3/DDP 中。在 SKOV3 细胞和 SKOV3/DDP 细胞中，过表达 FSTL1 后细胞活力降低，IC50 降低，DDP 敏感性提高。与空白组相比，FSTL1 组 SKOV3 细胞集落数量减少，细胞凋亡增加，FSTL1、Bax/Bcl-2 和 cleaved caspase-3 表达上调，p-IκBα、p-p65 和 survivin 表达下调。上调 FSTL1 与 DDP 联合处理还能有效降低 SKOV3/DDP 细胞集落形成，增加细胞凋亡，抑制 NF-κB 通路活性。此外，该联合处理还能显著抑制裸鼠皮下移植瘤的生长。
FSTL1 可能通过抑制 NF-κB 信号通路抑制上皮性卵巢癌细胞的生长，促进其凋亡，从而增强其对 DDP 的敏感性。
