Cationic liposome coupled endostatin gene for treatment of peritoneal colon cancer
Keng-Li Lan1, Fu Ou-Yang, Sang-Hue Yen
1Cancer Center, Taipei Veterans General Hospital, 11217, Taipei, Taiwan.
Abstract:
Therapy targeting cancer blood vessels requires unwavering pharmacokinetics of antiangiogenic therapeutics to neutralize the excess pro-angiogenic factors constantly secreted by tumor cells. Gene therapies have been explored to effectively create a microenvironment less favorable for angiogenesis and tumor expansion. In this study, we examined the inhibitory effect of cationic liposome coupled with the murine endostatin gene (Lipo/mEndo) on growth of intraperitoneal disseminated colon cancer models. Intraperitoneal injection of Lipo/mEndo inhibited bioluminescent signals emitted from CT26 colon cancer cells stably expressing luciferase in the living mice and prolonged their survival times. Endostatin gene therapy suppressed the colony forming capability and VEGF concentration of ascites obtained from treated mice by 74 and 60%, respectively. When tested in a similar model using HCT116 human colon cancer cells, Lipo/mEndo and bevacizumab displayed comparable repressive effects on ascites formation and tumor foci dissemination on mesentery of experimental mice. Our results implicate that cationic liposome coupled endostatin gene therapy may be a clinically effective treatment for intraperitoneal disseminated colon cancer.
Insights
Cationic liposome coupled with the murine endostatin gene effectively inhibited colon cancer growth in mice. This gene therapy reduced tumor spread and prolonged survival, showing promise for treating disseminated colon cancer.
Area of Science:
- Oncology
- Gene Therapy
- Nanomedicine
Background:
- Targeting tumor angiogenesis is crucial for cancer therapy.
- Gene therapy offers a strategy to modify the tumor microenvironment.
- Endostatin is a potent endogenous inhibitor of angiogenesis.
Purpose of the Study:
- To evaluate the efficacy of cationic liposome-mediated murine endostatin gene therapy (Lipo/mEndo) against intraperitoneal disseminated colon cancer.
- To assess the impact of Lipo/mEndo on tumor growth, metastasis, and survival.
- To compare Lipo/mEndo with bevacizumab in a human colon cancer model.
Main Methods:
- Intraperitoneal injection of Lipo/mEndo in mouse models of colon cancer (CT26 and HCT116).
- Monitoring tumor growth using bioluminescence imaging.
- Quantifying colony-forming capability and vascular endothelial growth factor (VEGF) concentration in ascites.
- Assessing tumor foci dissemination and survival rates.
Main Results:
- Lipo/mEndo significantly inhibited tumor growth and prolonged survival in CT26 colon cancer models.
- Endostatin gene therapy suppressed ascites colony formation by 74% and VEGF concentration by 60%.
- In HCT116 models, Lipo/mEndo demonstrated comparable efficacy to bevacizumab in reducing ascites and mesenteric tumor dissemination.
Conclusions:
- Cationic liposome-coupled endostatin gene therapy is effective against intraperitoneal disseminated colon cancer.
- This approach offers a potential clinical strategy for managing advanced colon cancer.
- Further investigation into Lipo/mEndo for clinical application is warranted.
