Inhibitory Effect And Its Mechanism Of ADAMTS8 On The Growth Of Human Colorectal Cancer Cells

Background: Colorectal cancer(CRC)is known for being a great threat to human health due to its high incidence and mortality.ADAMTS8 that belongs to the zinc metalloproteinases family acts as a tumor suppressor and is silenced by CpG methylation in several carcinomas through previous studies,but its functions in CRC remain unknown.Methods : 1.ADAMTS8 expression levels in CRC cell lines and primary tumor tissues were assessed using RT-PCR and qPCR.2.Biological functions affected by ADAMTS8 were estimated in vitro using CCK-8,colony formation,flow cytometry,transwell assays.Also,tumor xenograft in nude mice experiment was performed to verify its ability of growth in vivo.3.Western blot was used to explore the mechanisms of ADAMTS8 in CRC.Results: 1.We found that ADAMTS8 was silenced in CRC cell lines(6/7)and significantly down-regulated in primary tumor tissues compared with adjacent tissues.DNA methyltransferase inhibitor5-aza-2’-deoxycytidine restored its expression in LoVo cell line.2.Over-expression of ADAMTS8 suppressed cell proliferation and induced apoptosis.In addition,ADAMTS8 inhibited cell migration and invasion,and induced cell cycle arrest in G2/M phase.3.Over expression of ADAMTS8 led to the decrease of BCL-XL,phospho-GSK3β,β-catenin and c-myc as well as increase of cleaved caspase-9,Bax and PARP.Conclusions: ADAMTS8 may be considered as a functional tumor suppressor gene in CRC and has the potential to be developed as a valuable biomarker.