Open AccessKLF 5 strengthens drug resistance of ovarian cancer stem‐like cells by regulating survivin expression
Author(s) -
Dong Z.,
Yang L.,
Lai D.
Publication year - 2013
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12043
Subject(s) - survivin , ovarian cancer , gene silencing , cancer research , cisplatin , chromatin immunoprecipitation , cancer stem cell , cancer cell , chemistry , stem cell , cell culture , biology , cell growth , small interfering rna , cell , microbiology and biotechnology , cancer , transfection , gene expression , chemotherapy , biochemistry , gene , promoter , genetics
Abstract Objectives Ovarian cancer stem‐like cells ( CSC s), 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 ( KLF 5) is involved in cell proliferation and mediates cell survival and tumourigenesis. Here, we investigated the role of KLF 5 and its downstream target survivin, in strengthening drug resistance of ovarian CSC s. 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. si RNA ‐ KLF 5 was used to knock down KLF 5, 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 KLF 5 and survivin expression. Drug resistance was examined by MTT and apoptosis assays. Results KLF 5 was highly expressed in the ovarian cancer cell line SKOV 3 sphere cells, accompanied by elevated survivin expression. Silencing KLF 5 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 KLF 5 controlled survivin expression by directly binding the surivin promoter in the cells. Conclusions The KLF 5‐mediated signalling pathway is a potential target for elimination of ovarian CSC s.