ABSTRACT
Objective:To investigate the relationship of the mRNA expression of BRCA1 andβ-tubulinⅢwith docetaxel-resistance in esophageal cancer. Methods:The genes BRCA1 andβ-tubulinⅢwere determined at the mRNA level using RT-qPCR in 36 esophageal carcinoma specimens. Results:The mRNA expression of BRCA1 andβ-tubulinⅢwas determined in the 36 tumor samples using RT-qPCR. The median BRCA1 mRNA expression level in relation to that ofβ-actin was 6.27. The medianβ-tubulinⅢmRNA expression level in relation to that ofβ-actin was 4.44. The patients were divided into two groups using these cutoff values. The BRCA1 mRNA expression level was not correlated with the sensitivity of esophageal cancer patients to docetaxel (P=0.733). The response rate of the tumors with highβ-tubulinⅢexpression was (38.9%), which is significantly lower than in patients with lowβ-tubulinⅢexpression (83.3%) (P=0.015). Conclusion:Theβ-tubulinⅢexpression levels in the tumor tissues were probably an important biomarker for the efficacy of docetaxel chemotherapy in esophageal cancer patients. Our study may provide new insights into taxane chemotherapy for advanced esophageal cancer patients.
ABSTRACT
Objective To investigate the sequence-dependent effects of gemcitabine plus erlotinib on the proliferation of human pancreatic carcinoma cells,BXPC-3 and PANC-1,and the possible mechanisms involved.Methods The expressions of mRNA and protein of endothelial growth factor receptor(EGFR)were determined by RT-PCR and Western blotting respectively.MTT assay was used to examine the effects of gemcitabine(3?10-11-3?10-2mol/L)and erlotinib(10-8-10-4mol/L),respectively,on the proliferation of human pancreatic carcinoma cells,then the IC50 was calculated subsequently.The effects of gemcitabine(IC50)and erlotinib(10-5mol/L)either administered alone,simultaneously,or sequentially(with 72h or 24h interval)on the proliferation of cells with MTT assay.Cell cycle was detected by flow cytometry.Results Both mRNA and protein of EGFR were expressed in BXPC-3 and PANC-1 cells.Gemcitabine(3?10-10-3?10-2mol/L)and erlotinib(10-6-10-4mol/L)significantly inhibited the proliferation of BXPC-3 and PANC-1 cells in a time-and concentration-dependent manner.The effects of gemcitabine plus erlotinib on cell proliferation were sequence-dependent.The inhibitory effects on cell proliferation was enhanced when administered simultaneously(P=0.034;P=0.049)or erlotinib was administered 24h prior to gemcitabine(P=0.001;P=0.025)in comparison to that of each drug used alone.However,administration of erlotinib 24h after that of gemcitabine(P=0.499,P=0.824)exerted no additive effects on the cell proliferation when compared with the effect of gemcitabine used alone.No statistical difference existed in the inhibitory effects on cell proliferation between the simultaneous administration of both drugs and the gemcitabine administration following erlotinib(P=0.199,P=0.767).Erlotinib plus/or gemcitabine treatment resulted in the block of cell cycle of BXPC-3 cells at G1 phase.Conclusions Both gemcitabine and erlotinib can inhibit the proliferation of BXPC-3 and PANC-1 cells.The concurrent administration or sequential administration of gemcitabine following erlotinib exerts stronger additive effects on cell proliferation than when gemcitabine is used alone.However,the additive effects are not related to the influence of the both drugs on cell cycles.