BACKGROUD/AIM: We previously demonstrated that high protein expression of excision repair cross-complementation group-1 (ERCC1) was associated with poor disease-free survival in patients who received adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin, and was shown to be an independent prognostic factor. In the present study, we evaluated ERCC1 expression levels in uterine cervical adenocarcinoma cell lines to assess whether they are affected by treatment with cisplatin with and without 5-fluorouracil (5-FU).
Materials and methods: Firstly, half-maximal (50%) inhibitory concentration (IC50) values for cisplatin or 5-FU were calculated in cervical adenocarcinoma, HCA-1, and TCO-2 cell lines by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, yellow tetrazole (MTT) assay. ERCC1 mRNA and protein levels were investigated by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Secondly, cisplatin-resistant HCA-1 cells, designated HCA-1R cells were established, and IC50 values for cisplatin and 5-FU were calculated by the MTT assay. ERCC1 mRNA expression levels were investigated using quantitative RT-PCR following treatment with cisplatin with and without 5-FU.
Results: HCA-1 and TCO-2 cells exhibited similar sensitivity to cisplatin, and 5-FU, and comparable expression of ERCC1 mRNA and protein levels. HCA-1R cells exhibited two-fold higher resistance to cisplatin and a significantly higher level of ERCC1 mRNA expression compared to native HCA-1 cells. ERCC1 expression was significantly elevated by cisplatin treatment, which was reduced by co-administration of 5-FU in HCA-1, TCO-2 and HCA-1R cells.
Conclusion: The current study demonstrated an association between ERCC1 expression and sensitivity to cisplatin in cervical adenocarcinoma cells. Co-administration of cisplatin and 5-FU revealed synergistic or additive effects through inhibition of ERCC1 expression in cervical adenocarcinoma cells. Therefore, it is possible that a combination therapy of cisplatin and 5-FU or 5-FU derivatives constitutes an ideal treatment regimen, from the ERCC1 inhibition point of view in cervical adenocarcinoma.
Keywords: 5-FU; Cervical adenocarcinoma; ERCC1; HCA-1; HCA-1R cells; TCO-2; chemosensitivity; cisplatin.