Fascaplysin exert anti-tumor effects through apoptotic and anti-angiogenesis pathways in sarcoma mice model

Abstract

Previous studies indicated that fascaplysin derived from marine sponge can induce tumor cell death by apoptosis and possesses anti-angiogenesis activity. In order to verify these two effects in animal model and to identify action mechanisms, we established a sarcoma mice model, and treated mice with fascaplysin for 10 days. The tumor tissues were examined morphologically and immunohistochemically. The differential gene expression was also investigated by mRNA array. Fascaplysin treatment resulted in a significant suppression of tumor growth. Typical apoptotic phenomena were observed by transmission electron microscope and histological detection. Tissue sections were stained with monoclonal antibody directed to proliferating cell nuclear antigen (PCNA) and CD31. The decreased PCNA and CD31 antigen staining indicate the reduction of tumor cell proliferation and tumor vasculature property of fascaplysin in vivo. Microarrays were used to examine the gene expression profiles of tumors on CapitalBio mouse genome oligo array. The regulated genes analyzed from the expression level showed overlapping gene ontology (GO) categories and pathway mapping. Our findings indicate that cell cycle arrest, apoptosis, regulation of actin cytoskeleton, and cell adhesion all play important roles in the onset of fascaplysin. Detailed analysis by real time PCR of key genes confirmed the experimental results of microarrays. From these findings, it can be considered that fascaplysin can inhibit the growth of S180 cell implanted tumor, and the action mechanisms may involve in apoptosis, anti-angiogenesis, or cell cycle arrest.