Abstract. We have shown that an antimicrobial peptide (AMP) cecropinXJ isolated from the larvae of Bombyx mori selectively inhibits the proliferation of cancer cells. However, the mechanism remains to be determined. In the present study, we examined the antitumor activity of cecropinXJ against human gastric cancer BGC823 cells and explored the mechanism. The results showed that cecropinXJ inhibited the growth of gastric cancer BGC823 cells in vitro and in vivo. MTT and colony formation assays indicated that cecropinXJ suppressed cell proliferation and reduced colony formation of BGC823 cells in a dose-and time-dependent manner, but without inhibitory effect on normal gastric epithelia GES-1 cells. S-phase arrest in BGC823 cells was observed after treatment with cecropinXJ. Annexin V/PI staining suggested that cecropinXJ induced both early and late phases of apoptosis through activation of mitochondrial-mediated caspase pathway, upregulation of Bax expression and downregulation of Bcl-2 expression. Additionally, cecropinXJ treatment increased reactive oxygen species (ROS) production, disrupted the mitochondrial membrane potential (Δψ m ) and led to release of cytochrome c. Importantly, in vivo study showed that cecropinXJ significantly prevented the growth of xenograft tumor in the BGC823-bearing mice, possibly mediated by the induction of apoptosis and inhibition of angiogenesis. These results suggest that cecropinXJ may be a promising therapeutic candidate for the treatment of gastric cancer.
IntroductionGastric cancer is one of the most common malignant tumors, >70% of new cases and deaths occur in developing countries each year (1). In China, the incidence and mortality rate of gastric cancer are increasing. Although there are distinct discrepancies in diagnosis, prognosis, and treatment efficacy for gastric cancer patients, the 5-year survival rate of gastric cancer is generally <20% (2). At present, the management of gastric cancer includes surgery, radiotherapy, conventional chemotherapy, molecular targeted therapy and biological therapy, but these methods have not reached expected clinical efficacy, which mainly focus on mass cell killing without high specificity and often causes severe side-effects and toxicities. Moreover, recurrences and metastasis frequently occur in the majority of patients (2). Hence, it is urgent to explore safe and effective therapeutic agents for gastric cancer to improve the survival rate and quality of life.Antimicrobial peptides (AMPs) are evolutionarilyconserved components of the innate immune system (3), which exert their activities against a broad range of microbial pathogens. Compared to conventional treatments, AMPs have many advantages, such as specific cytotoxicity for cancer cells, ability to bypass the multidrug-resistance mechanism, and additive effects in combination therapy (4), suggesting that AMPs has potential as a novel antitumor agent for the treatment of cancer.AMPs can directly kill cancer cells by a cell membranelytic effect (5), or trigger apoptosis in can...