Mutant Bik gene transferred by cationic liposome inhibits peritoneal disseminated murine colon cancer

Abstract

Peritoneal carcinomatosis of intraabdominal malignancies, such as pancreatic, ovarian, gastric, and colorectal cancers, represents an unmet medical need as conventional cancer treatments rarely eliminate these tumors. Satisfactory treatment for either peritoneally disseminated tumors or prevention of local recurrence after surgery is yet to be developed. To improve the efficacy of novel strategies against peritoneal metastasis, a sensitive, and less invasive model is needed to scrutinize the in vivo tumor growth and response to experimental therapeutics. To study this we intraperitoneally inoculated CT-26 stably expressing luciferase (CT-26-Luc) to mimic tumor spreading within the abdomen. Bioluminescent signals emitted from the living experimental mice correlate well with the injected cell numbers as well as the weights of dissected tumors. Since a nonviral cationic liposome coupled mutant pro-apoptotic gene, Bik(T33D/S35D) (BikDD), was previously shown to have potent anti-cancer effects on an orthotopic breast cancer animal model (Li et al., Cancer Res 63(22):7630-7633, 2003), we evaluated the inhibitory effect of BikDD on the growth kinetics of intraperitoneally inoculated CT-26-Luc. We found that intraperitoneal (i.p.) injection of liposome coupled BikDD suppressed the expansion of CT-26-Luc and prolonged life span of experimental mice. These results suggest a therapeutic effect of BikDD gene therapy on peritoneal carcinomatosis of colon cancer.