Mutant Bik gene transferred by cationic liposome inhibits peritoneal disseminated murine colon cancer
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Updated: Jul 13, 2026
Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer
Published on: July 18, 2017
Keng-Li Lan1, Sang-Hue Yen, Ren-Shyan Liu
1Cancer Center, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
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.
Insights
Peritoneal carcinomatosis, a challenge in abdominal cancers, was targeted using BikDD gene therapy. This approach showed promise in suppressing tumor growth and extending survival in a preclinical colon cancer model.
Area of Science:
- Oncology
- Gene Therapy
- Cancer Metastasis
Background:
- Peritoneal carcinomatosis from intraabdominal malignancies is difficult to treat with conventional therapies.
- Effective treatments for peritoneal metastasis and prevention of recurrence are lacking.
- A sensitive, less invasive preclinical model is needed to study peritoneal tumor growth and therapeutic responses.
Purpose of the Study:
- To establish a bioluminescent mouse model for peritoneal carcinomatosis.
- To evaluate the therapeutic potential of BikDD gene therapy against colon cancer peritoneal metastasis.
Main Methods:
- CT-26 colon cancer cells stably expressing luciferase were inoculated intraperitoneally in mice.
- Bioluminescence imaging was used to monitor tumor growth and correlate with tumor weight.
- Liposome-coupled mutant pro-apoptotic gene BikDD (BikDD) was administered via intraperitoneal injection.
Main Results:
- Bioluminescent signals accurately reflected tumor burden in vivo.
- Intraperitoneal injection of liposome-coupled BikDD significantly suppressed CT-26-Luc tumor expansion.
- BikDD treatment prolonged the survival of mice with peritoneal carcinomatosis.
Conclusions:
- The CT-26-Luc mouse model effectively mimics peritoneal carcinomatosis.
- BikDD gene therapy demonstrates therapeutic efficacy against colon cancer peritoneal metastasis.
- BikDD holds potential as a treatment for peritoneal carcinomatosis.
