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Published on: September 18, 2013
Electrogene therapy using endostatin, with or without suicide gene therapy, suppresses murine mammary tumor growth
M-A Shibata1, J Morimoto, H Doi
1Department of Anatomy and Cell Biology, Division of Basic Medicine I, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka, Japan. shibatam@art.osaka-med.ac.jp
Abstract:
Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of a plasmid vector containing either endostatin (pEndo) with or without a suicide gene (pHSVtk), pHSVtk alone or control vector once a week for 8 weeks. We applied electrogene transfer to the tumors after each injection and administered ganciclovir (GCV) to pHSVtk-transfected mice using an osmotic minipump. Anticancer efficacy was monitored using a variety of parameters, namely tumor volume, intratumoral microvessel density and DNA synthesis, number of mice with metastasis, and number of sites of metastasis per mouse. Tumor volume was significantly lower in all therapeutic groups, with the most effective growth suppression in the pEndo+pHSVtk/GCV group. Lymph node metastasis was significantly less frequent in all therapeutic groups, whereas the multiplicity of lung metastases was significantly lower only in the pEndo and pEndo+pHSVtk/GCV groups. All therapeutic groups showed significantly lower intratumor microvessel density and DNA synthesis. The pEndo and pEndo+pHSVtk/GCV groups also showed a significant reduction in the numbers of dilated lymphatic vessels containing intralumenal tumor cells. Our data suggest that endostatin electrogene therapy alone or in combination with pHSVtk/GCV suicide gene therapy is more beneficial than suicide gene therapy alone. The observed antimetastatic activity of endostatin may be of high clinical significance in the treatment of metastatic breast cancer.
Insights
Endostatin gene therapy, alone or with suicide gene therapy, effectively suppressed metastatic breast cancer growth and spread in mice. Combination therapy showed the greatest anticancer efficacy.
Area of Science:
- Oncology
- Gene Therapy
- Cancer Metastasis
Background:
- Metastatic breast cancer remains a significant clinical challenge.
- Novel therapeutic strategies targeting tumor growth and metastasis are urgently needed.
Purpose of the Study:
- To evaluate the efficacy of endostatin electrogene therapy, alone or combined with pHSVtk/ganciclovir suicide gene therapy, in a syngeneic model of metastatic breast cancer.
- To assess the impact of these therapies on tumor volume, metastasis, and tumor microenvironment.
Main Methods:
- Syngeneic metastatic mammary tumors were treated with intratumoral injection of plasmid vectors encoding endostatin (pEndo) and/or a suicide gene (pHSVtk) using electrogene transfer.
- Mice received weekly treatments for 8 weeks, with ganciclovir (GCV) administered to pHSVtk-transfected groups.
- Anticancer efficacy was assessed by measuring tumor volume, microvessel density, DNA synthesis, and metastatic burden.
Main Results:
- All therapeutic groups showed significant reductions in tumor volume, microvessel density, and DNA synthesis.
- Endostatin electrogene therapy (pEndo), alone or combined with pHSVtk/GCV, demonstrated superior efficacy in suppressing tumor growth and reducing lung metastasis.
- Combination therapy (pEndo+pHSVtk/GCV) yielded the most significant growth suppression and antimetastatic effects.
Conclusions:
- Endostatin electrogene therapy exhibits potent anticancer and antimetastatic activity in metastatic breast cancer.
- Combining endostatin gene therapy with suicide gene therapy offers enhanced therapeutic benefits.
- These findings highlight the clinical potential of endostatin-based gene therapies for managing metastatic breast cancer.
