KLF5 strengthens drug resistance of ovarian cancer stem-like cells by regulating survivin expression.

OBJECTIVES

Ovarian cancer stem-like cells (CSCs), which can form non-adherent sphere cells in a stem-cell selection culture system, exhibit stemness and drug resistance to chemotherapeutics, which are properties not observed in differentiated cells. Recent studies have demonstrated that Kruppel-like factor 5 (KLF5) is involved in cell proliferation and mediates cell survival and tumourigenesis. Here, we investigated the role of KLF5 and its downstream target survivin, in strengthening drug resistance of ovarian CSCs.

MATERIALS AND METHODS

Ovarian cancer cell line SKOV3 was cultured under serum-free conditions and differentiating conditions to promote formation of sphere cells and differentiated cells, respectively. siRNA-KLF5 was used to knock down KLF5, and survivin expression vector was used to overexpress survivin. Cells were further analysed by qPCR, immunofluorescence staining and western blotting. Chromatin immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA) were performed to investigate the relationship between KLF5 and survivin expression. Drug resistance was examined by MTT and apoptosis assays.

RESULTS

KLF5 was highly expressed in the ovarian cancer cell line SKOV3 sphere cells, accompanied by elevated survivin expression. Silencing KLF5 by small interfering RNA in sphere cells down-regulated survivin expression, which also sensitized the sphere cells to apoptosis induced by chemotherapeutic drugs (cisplatin or paclitaxel). Furthermore, ChIP assay, survivin overexpression and EMSA results indicated that KLF5 controlled survivin expression by directly binding the surivin promoter in the cells.

CONCLUSIONS

The KLF5-mediated signalling pathway is a potential target for elimination of ovarian CSCs.