Anti-tumor Effect Of Mere15, A Novel Polypeptide From Meretrix Meretrix

Lung cancer is the leading cause of cancer-related deaths worldwide andnonsmall cell lung carcinomas (NSCLC) account for approximately80%of lungcancer cases. Over the past decade, a number of new agents have been used to prolongsurvival and to improve life quality of NSCLC patients. Despite advances in surgeryand adjuvant therapy, most anticancer agents cause severe side effect and treatment ofNSCLC is still a challenging issue in the clinical setting. Thus, new anti-lung cancerdrugs are still badly in need. The marine environment is a rich resource fordiscovering novel biologically active compounds. Marine organisms provide hugeamounts of natural products with biological activities.Mere15is a novel polypeptide extracted from M. meretrix. MTT assay showedthat Mere15displayed anti-cancer activity in vitro, with the IC50of34.90g/mL. Cellmorphological changes were observed under an inverted microscope, and we foundthat cells treated with Mere15became spherical and detached from the plate wallquickly. The number of round cells increased in a dose-dependent manner. Andcytoplasmic vacuoles could be found in the rounded injured cells under the highpower microscopic.In order to elucidate the anti-cancer mechanism of Mere15, we furtherinvestigated the inhibition effect of Mere15on cell adhesion, migration and invasion.In the Cell Adhesion Assay, we found that when treating the cells with12.0g/mL ofMere15, the adhesion ability of A549cells on ECM and Fn were reduced by86.74%and50.56%, respectively. The effect of Mere15on cell migration and invasion wereinvestigated by Transwell Assay. Results showed that the abilities of A549cellmigration and invasion were decreased by the polypeptide with the inhibition ratio of69.22%and53.84%at the concentration of15g/mL. Matrix metalloproteinases(MMPs) are a large family of zinc-dependent proteases which play an essential role incancer metastasis. The secretion and expression of MMPs were observed by GelatinZymography and RT-PCR, and the results revealed that the secretion of MMP-2and MMP-9were significantly inhibited and the mRNA expression of MMP-2andMMP-9were also down-regulated in A549cells treated with Mere15. The studydemonstrates that the anti-metastasis effect of Mere15was perhaps correlated with theinhibition of the secretion and expression of MMPs.