Effects Of Recombinant Human Canstatin Protein And Oncolytic Adenovirus He-Cans In The Treatment Of Pancreatic Cancer

The purpose of the present study is to develop new treatment strategy for pancreatic cancer through combining anti-angiogenesis therapy with gene therapy. The canstatin gene cDNA was amplified by RT-PCR from the total RNA extracted from human placenta, and was inserted into plasmid pET-22b(+) to construct prokaryotic expression vector pET/canstatin, which was induced to express Canstatin protein by IPTG after transformed into E. coli BL21. Our findings demonstrate that Canstatin protein effectively retards the growth of pancreatic cancer through inhibiting angiogenesis in vivo. Then, canstatin gene was inserted into vector pCA13 and pXC7C to construct shutter vector pCA13-Cans and pXC7C-Cans, which were co-transfected with pBHGE3 separately into 293 cells to produce new recombinant replication incompetent and competent adenoviruses, named as Ad5-Cans and He-Cans respectively. The results of the in vitro and in vivo experiments show that adenovirus He-Cans efficiently inhibits the growth of pancreatic cancer, far more potent than adenovirus Ad5-Cans and Canstatin protein without remarkable adverse effects, showing a promising future in its clinical application. The main mechanisms of its anti-tumor effect include anti-angiogenesis effect by expressing Canstatin protein and oncolytic effect by replicating selectively in tumor cells.