Abstract 2056: Anticancer bioactive peptide potentiates cisplatin chemotherapy efficacy to improve the quality of life in xenografted nude mice bearing human gastric cancer.

Abstract

Abstract A great challenge of cancer chemotherapy is to eliminate cancer cells and concurrently maintain the quality of life (QOL) for cancer patients. We previously found that anticancer bioactive peptide (ACBP) alone exhibited anti-tumor activity without measurable side effects. Thus, we hypothesize that ACBP and combined chemotherapy could lower the drug dose and improve the efficacy of treatment, leading to a better QOL. In this study, ACBP was isolated and purified from goat liver, and designated as ACBP-L. The anti-tumor activity of ACBP-L was titrated on human gastric cancer MGC-803 cell line in vitro by MTT assay, and its effect on cell morphology was observed through light and scanning electron microscopy. In vivo, MGC-803 tumors were grown in a xenograft nude mouse model, the body weight, food intake, volume and weight of tumors were measured. 18F- FDG PET/CT scan was used to examine the biological activity in tumors of live animals. Expression of Bcl-2, Bax, Caspase 3 and Caspase 8 in the tumor specimens was examined by RT-PCR and immunohistochemistry. Herein, we showed that ACBP-L inhibited MGC-803 cells in a dose and time dependent manner in vitro. In the MGC-803 xenograft nude mouse model, ACBP-L alone significantly inhibited tumor growth in vivo without measurable side effects. Treatment with the full dosage of Cisplatin alone (5mg/kg every 4 days) strongly suppressed tumor growth; however, the QOL in these mice had been significantly affected when measured by food intakes and body weight. The combinatory regiment of ACBP-L with a fewer doses of Cisplatin (5mg/kg every 10 days) resulted in a similar anti-tumor activity with improved QOL. The tumor tissues were harvested after treatment, and ACBP-L suppressed Bcl-2, and induced Bax, Caspase 3, and Caspase 8 protein expression more significantly than in the tissues harvested from Cisplatin alone treatment as detected by immunohistochemistry. The combinatory regiment induced stronger gene expression of Bax and Caspase 8. Our data demonstrated that ACBP-L could lower Cisplatin dose to achieve a similar anti-tumor efficacy as the higher dose of Cisplatin alone. This combined regiment improved QOL in the xenograft gastric cancer model through the modulation of apoptotic molecules. Citation Format: Xiulan Su, Chao Dong, Liya Su, Jialing Zhang, Xuemei Wang, Xia Bai, Hongwei Cui, Zhong Chen. Anticancer bioactive peptide potentiates cisplatin chemotherapy efficacy to improve the quality of life in xenografted nude mice bearing human gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2056. doi:10.1158/1538-7445.AM2013-2056