Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells
Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells
AbstractCancer cells often develop drug resistance. In cisplatin-resistant HeLa cisR cells, fibroblast growth factor 13 (FGF13/FHF2) gene and protein expression was strongly upregulated and intracellular platinum concentrations were kept low. When the FGF13 expression was suppressed, both the cells' resistance to platinum drugs and their ability to keep intracellular platinum low were abolished. Overexpression of FGF13 in parent cells led to greater resistance to cisplatin and reductions in the intracellular platinum concentration. These cisplatin-resistant cells also showed increased resistance to copper. In preoperative cervical cancer biopsy samples from poor prognoses patients after cisplatin chemoradiotherapy, FGF13-positive cells were detected more abundantly than in the biopsy samples from patients with good prognoses. These results suggest that FGF13 plays a pivotal role in mediating resistance to platinum drugs, possibly via a mechanism shared by platinum and copper. Our results point to FGF13 as a novel target and useful prognostic guide for cancer therapy.
Adult, Uterine Cervical Neoplasms, Antineoplastic Agents, Middle Aged, Article, Up-Regulation, Fibroblast Growth Factors, Gene Expression Regulation, Neoplastic, Alternative Splicing, Treatment Outcome, Drug Resistance, Neoplasm, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Female, RNA, Messenger, Cisplatin, HeLa Cells, Neoplasm Staging
Adult, Uterine Cervical Neoplasms, Antineoplastic Agents, Middle Aged, Article, Up-Regulation, Fibroblast Growth Factors, Gene Expression Regulation, Neoplastic, Alternative Splicing, Treatment Outcome, Drug Resistance, Neoplasm, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Female, RNA, Messenger, Cisplatin, HeLa Cells, Neoplasm Staging
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