Antitumor and antimetastatic activities of vesicular stomatitis virus matrix protein in a murine model of breast cancer

Abstract

Vesicular stomatitis virus (VSV) matrix protein (MP) is capable of inducing in vitro apoptosis of tumor cells in the absence of other viral components. Here, we report the potent antitumor and antimetastatic effects of recombinant plasmid pVAX-MP complexed with cationic liposome (DOTAP:Chol) against highly metastatic 4T1 mammary tumor. Mice with 10-day established 4T1 metastatic carcinomas showed a significant reduction in spontaneous lung metastases as well as an evident inhibition in the growths of primary tumors yet without conspicuous systemic toxic effects following a 35-day course of intravenous therapy with pVAX-MP:liposome complexes once every 5 days; the therapy significantly prolonged the survival of the tumor-bearing mice consequently. The histomorphometric analysis revealed an increased percent apoptosis and decreased expression of MMP-9 in pVAX-MP:liposome complexes group. In summary, these results indicate that pVAX-MP:liposome complexes have the ability to inhibit the growths and metastases of mouse breast cancer and they may be a novel and potentially effective therapy against human advanced breast cancer.