Gene Therapy for Colorectal Cancer by Changing Fatty Acids Composition of Cell Membrane / 中国肿瘤临床

ABSTRACT

Objective: To explore the effect of the fat-1 gene encoding n-3 fatty acid desaturase on the proliferation and apoptosis of human colon cancer cell line HT-29 and to explore its value in the gene therapy for colorectal cancer. Methods: The fat-1 gene was cloned into adenovirus shuttle vector pAd-CMV and then recombinated with backbone vector to con-struct a recombinant adenoviral vector pAd.GFP.fat1. The vector was transfected into 293 cells to get the recombinant virus infected human colon cancer cell line HT-29. Total RNA of the cells was analyzed by Northern blot. The effect of fat-1 gene on the proliferation and apoptosis of the infected cells was analyzed by flow cytometry. The content of n-6PUFAs/n-3PUFAs was analyzed by Gas Chromatography. The anti-cancer effect of fat-1 gene was studied on HT-29 xenografts in nude mice in vivo. Results: The high titer recombinant virus was obtained. Fat-1 gene can be highly expressed in human colon cancer call line HT-29. Compared with that of the control cells (Ad.GFP), proliferation of HT-29 cells was inhibited by fat-1 gene. Fat-1 gene can lower the ratio of n-6/n-3PUFAs. The growth of tumors in nude mice is also inhibited by fat-1 gene. Conclu-sion Fat-1 gene is of great value in the gene therapy for colorectal cancer.