Research Of Correlation Between ERCC1, Ratio TP/DPD And Chemosensitivity For Gastric Cancer In Vitro

BackgroundIn spite of the increasingly dropping morbidity and mortality, gastric cancer is still globally the principal killer as well as an important health issue, surgery is the golden standard for treatment of gastric cancer. Nevertheless, the long-term result was suboptimal due to40-60%recurrence rate. Chemotherapy plays an important role in treatment of gastric cancer, the option of chemotherapy regimen choosed by the physicians is subject to NCCN guideline, combination of platinum and Fluorouracil plays an important role in chemotherapy for gastric cancer, but several researches demonstrated that overall response rates were less than50%in gastric cancer patients treated with various of regimens. For patients who didn’t get benefits from chemotherapy, treatments were delayed actually. It is possible to predict chemosensitivity via finding correlations between expression level of drug-resistent genes and chemosensitivity, but there were no consistent conclusions. How to choose appropriate drug-resistent genes to predict effects of chemotherapy becomes a research focus.Objective Combination of platinum and Fluorouracil was widly used in chemotherapy for gastric cancer. Our purpose was to study the correlations of excision repair cross-complementing group1(ERCC1), ratio TP/DPD in multi gastric cancer cell lines with effect of chemotherapeutic drugs, and to evaluate if these factors were appropriate to predict effects of chemotherapy in clinical researches. We maked a tentative exploration on whether ERCC1or TP/DPD could be used for evaluating the effect of combination of cisplatin and5-DFUR.Methodology6gastric cancel cell lines and GES cell line were cultured conventionally; mRNA expression levels without drugs of ERCC1, TP, DPD and ratio TP/DPD of gastric cancer cell lines were detected by Real-time PCR, and ERRC1protein expression levels without drug were detected by Western Blot; cells were cultured for6h,12h,24h and48h by adding different concentrations of cisplatin or5-DFUR respectivily, and were cultured for48h by adding combination of two drugs, and then cells viability were detected by CCK-8to calculate inhibitory concentration50(IC50), and for correlations, the Spearman’s p(r) was calculated.Results1. After24h and48h, ERCC1mRNA expression levels and IC50(cisplatin) showed a possitive correlation (ρ(24h)=0.89, P(24h)=0.019, ρ(48h)=0.94, P(48h)=0.005), ERCC1protein and IC50(cisplatin) showed no correlation, and there was no correlation between ERCC1and IC50(5-DFUR). Cell lines with lower ERCC1mRNA were more sensitive to cisplatin. ERCC1was not associated with IC50(5-DFUR)(P>0.05).2. After24and48hours, mRNA of ratio TP/DPD and IC50(5-DFUR) showed a negtive correlation (ρ(24h)=-0.829, P(24)=042, ρ(48h)=-0.829, P(48h)=0.042), cell lines with higher ratio of TP/DPD were more sensitive to5-DFUR, but there was no correlation between TP/DPD and IC50(cisplatin). TP, DPD associated with neither IC50(cisplatin) nor mRNA of IC50(5-DFUR).3. After48h of combination of cisplatin and5-DFUR, ERCC1, TP, DPD and ratio TP/DPD were not associated with IC50(drug combination).Conclusion1. Lower ERCC1mRNA level was associated with higher sensitivity to cisplatin, and it may be a usefully factor to predict sensitivity to cisplatin for gastric cells.2. Higher ratio of TP/DPD level was associated with higher sensitivity to5-DFUR, and it may be a usefully factor to predict sensitivity to5-DFUR for gastric cells.3. ERCC1, TP, DPD and ratio TP/DPD were not associated with sensitivity to combined regimen of cisplatin and5-DFUR, and it is not appropriate to evaluate effect of this combined regimen by these factors.