New bioactive peptide reduces the toxicity of chemotherapy drugs and increases drug sensitivity

作者：Li, Xian; Wu, Huijun; Ouyang, Xiaohui; Zhang, Bo; Su, Xiulan^*

来源：Oncology Reports, 2017, 38(1): 129-140.

DOI：10.3892/or.2017.5674

• anticancer peptide activity
• oxaliplatin
• gastric cancer
• nude mouse xenograft

Anticancer bioactive peptide (ACBP) is extracted from normal goat spleens and exhibits antitumor activity alone and in combination with low cisplatin doses to achieve antitumor efficacy similar to higher cisplatin doses via sustained medication modes. In the present study, we investigated whether elevated levels of induced or normal ACBP in MKN-45 gastric cancer (GC) cells may reduce their toxicity to oxaliplatin (L-OHP) in a dose-dependent manner. The growth inhibition rate (IR), morphological changes and gene expression were examined in MKN-45 GC cells. Compared with normal ACBP, induced ACBP alone significantly enhanced the anticancer activity of L-OHP-mediated apoptosis and reduced the amount and side-effects of L-OHP (P<0.05). The inhibition of cancer cell growth at high concentrations of induced ACBP and L-OHP was significantly more effective than at low concentrations. In addition, for the first time, we examined the potential of a combination of induced ACBP and L-OHP to increase L-OHP sensitivity in human gastric carcinoma xenograft tumors. Nude mice were implanted with human gastric carcinoma MKN-45 cells and treated with an intraperitoneal injection of 0.5 ml of normal saline, 30 mu g/ml ACBP, 20 mu g/ml L-OHP or 30 mu g/ml ACBP + 20 mu g/ml L-OHP [combination of anticancer bioactive peptide and oxaliplatin (A+L)] via the tail vein twice a week. In vivo short-term intermittent use of induced ACBP alone significantly inhibited MKN-45 tumor growth. The combination of induced ACBP and L-OHP also significantly improved the quality of life of the nude mice and reduced the toxicity of L-OHP. Based on flow cytometry and gene expression analyses, A+L significantly increased the proportion of cells in the G2/M phase (P<0.05) relative to ACBP or L-OHP alone, and short-term intraperitoneal injection of ACBP increased the sensitizing effect of L-OHP. Collectively, these results suggest that high levels of induced ACBP in combination with L-OHP via a short-term intermittent medication mode could be a useful clinical therapeutic strategy for GC.

• 出版日期2017-7
• 单位内蒙古医科大学