Abstract
Cancer 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.
Highlights
In this report we show that FGF13/FHF2 plays a pivotal role in cellular platinum drug resistance and in reducing intracellular platinum concentrations in cancer cells
Our present findings indicate that upregulated FGF13 expression plays a pivotal role in the resistance of HeLa cisR cells to platinum anticancer drugs, and that the resistance reflects a reduction in the drugs’ intracellular concentrations
In some cases cisplatin efflux may be mediated by ATP-binding cassette (ABC) transporters (ABCs) such as P-glycoprotein (i.e., ABCB1)[19]
Summary
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. 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. In this report we show that FGF13/FHF2 plays a pivotal role in cellular platinum drug resistance and in reducing intracellular platinum concentrations in cancer cells. We believe our report to be the first to document a clear biological function of FGF13/FHF2 in drug resistance
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