Antitumor and antimetastatic activities of vesicular stomatitis virus matrix protein in a murine model of breast cancer.
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.
Shi
Wei
W
National Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
Tang
Qingqing
Q
Chen
Xiancheng
X
Cheng
Ping
P
Jiang
Peidu
P
Jing
Xiaomei
X
Chen
Xiang
X
Chen
Ping
P
Wang
Yongsheng
Y
Wei
Yuquan
Y
Wen
Yanjun
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000187:drug effects; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; C094460:M protein, Vesicular stomatitis virus; D014763:Viral Matrix Proteins; D020780:Matrix Metalloproteinase 9