Shi Wei, Tang Qingqing, Chen Xiancheng, Cheng Ping, Jiang Peidu, Jing Xiaomei, Chen Xiang, Chen Ping, Wang Yongsheng, Wei Yuquan, Wen Yanjun
National Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
J Mol Med (Berl). 2009 May;87(5):493-506. doi: 10.1007/s00109-009-0444-5. Epub 2009 Mar 4.
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.
水泡性口炎病毒（VSV）基质蛋白（MP）在无其他病毒成分的情况下能够在体外诱导肿瘤细胞凋亡。在此，我们报道了与阳离子脂质体（DOTAP:Chol）复合的重组质粒pVAX-MP对高转移性4T1乳腺肿瘤的强效抗肿瘤和抗转移作用。患有已形成10天的4T1转移性癌的小鼠，在每5天静脉注射一次pVAX-MP:脂质体复合物进行35天的治疗后，自发性肺转移显著减少，原发性肿瘤生长明显受到抑制，且无明显的全身毒性作用；该治疗因此显著延长了荷瘤小鼠的生存期。组织形态计量学分析显示，pVAX-MP:脂质体复合物组的凋亡百分比增加，MMP-9表达降低。总之，这些结果表明pVAX-MP:脂质体复合物有能力抑制小鼠乳腺癌的生长和转移，它们可能是一种针对人类晚期乳腺癌的新型且潜在有效的治疗方法。
