Abstract
The aim of the present study was to explore the effect of esophageal cancer-related gene 2 (ECRG2) protein in combination with cisplatin (DDP) on the proliferation and apoptosis of esophageal cancer cells. A 3-(4, 5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay was used to examine the effects of ECRG2 alone and ECRG2 in combination with DDP on the proliferation of EC9706 esophageal cancer cells. Hoechst 33258 staining was performed to analyze the effects of ECRG2 alone and ECRG2 in combination with DDP on apoptosis in the EC9706 cells. The expression levels of Bcl-2-associated X protein (Bax) mRNA and protein were determined by reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. The results from the MTT assay revealed that ECRG2 inhibited the proliferation of EC9706 cells and that ECRG2 in combination with DDP had a greater inhibitory effect on cell proliferation. The antiproliferative effects were time- and concentration-dependent, within a certain range of concentrations. The Hoechst 33258 staining results demonstrated that the number of apoptotic cells following treatment with ECRG2 in combination with DDP for 24 h was higher than that following treatment with ECRG2 alone for the same duration. Western blot analysis and RT-PCR results revealed that the expression levels of Bax mRNA and protein were upregulated in cells treated with ECRG2 in combination with DDP compared with those in cells treated with ECRG2 alone. Thus, ECRG2 in combination with DDP had an enhanced inhibitory effect on EC9706 cell proliferation compared with that of ECRG2 alone, and an increased inductive effect on EC9706 cell apoptosis, possibly due to the upregulation of the expression of Bax.
Highlights
At present, esophageal cancer has one of the highest morbidity and mortality rates, as well as one of the poorest prognosis rates, of all cancers worldwide, with >480,000 new cases and 400,000 mortalities annually [1]
Chemotherapy is able to improve the outcome of esophageal cancer [4,5], drug resistance and the side‐effects of chemotherapy are the main reasons for therapeutic failure and the high mortality rate of esophageal cancer
Cell apoptosis induced by esophageal cancer‐related gene 2 (ECRG2) and ECRG2 in combination with DDP, the expression levels of Bcl-2-associated X protein (Bax) mRNA in the esophageal cancer cells were studied by reverse transcription polymerase chain reaction (RT-PCR) analysis
Summary
Esophageal cancer has one of the highest morbidity and mortality rates, as well as one of the poorest prognosis rates, of all cancers worldwide, with >480,000 new cases and 400,000 mortalities annually [1]. Cisplatin (DDP) is a drug that is commonly used for treatment of a number of cancers, including esophageal cancer [6]. DDP has been used as an important agent in the treatment of esophageal cancer patients, its clinical application and efficacy have been limited due to side‐effects, including neurotoxicity, hearing loss and nephrotoxicity, and the emergence of drug resistance [7]. To the best of our knowledge, only one study [11] has been published to date on the combined effect of DDP and ECRG2 in the treatment of esophageal cancer. In the present study, the effects of ECRG2 in combination with DDP on EC9706 esophageal cell proliferation and apoptosis were investigated and compared with those of ECRG2 alone. The effects of the combination treatment on the expression levels of Bcl-2‐associated X protein (Bax) mRNA and proteins in the EC9706 cells were investigated
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