Antitumor and antimetastatic activities of vesicular stomatitis virus matrix protein in a murine model of breast cancer
- 191 Downloads
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.
KeywordsVesicular stomatitis virus matrix protein 4T1 mammary tumor Metastases DOTAP:Chol Apoptosis
Wei Shi, Qingqing Tang, Xiancheng Chen, Peidu Jiang, Xiaomei Jing and Yongsheng Wang devoted to the experimental work, data analysis and manuscript writing; Ping Cheng, Xiang Chen, Ping Chen contributed to the construction of expression vector and the preparation of liposome; Yanjun Wen and Yuquan Wei were engaged in devising project.
This work was supported by National 973 Project (No. 2004CB518807) and High-tech Research and Development Program (863 Program) of China (No. 2007 AA021106).
Competing interest statement
- 1.World Health organization (February 2006) Fact sheet No 297: CancerGoogle Scholar
- 6.Pulaski BA, Terman DS, Khan S (2000) Cooperativity of staphylococcal aureus entertoxin B superantigen, Major Histocompatibility Complex Class II, and CD80 for immunotherapy of advanced spontaneous metastases in a clinically relevant postoperative mouse breast cancer model. Cancer Res 60:2710–2715PubMedGoogle Scholar
- 31.Yuan H, Yoza BK, Lyles DS (1998) Inhibition of host RNA polymerase II-dependent transcription by vesicular stomatitis virus results from inactivation of TFIID. Virol 251:83–92Google Scholar
- 32.Yuan H, Puckett S, Lyles DS (2001) Inhibition of host transcription by vesicular stomatitis virus involves a novel mechanism that is independent of phosphorylation of TATA-binding protein (TBP) or association of TBP with TBP-associated factor subunits. J Virol 75:4453–4458CrossRefPubMedGoogle Scholar
- 45.Hlatky L, Hahnfeldt P, Folkman J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. J N C I 94:883–893Google Scholar