Open AccessCombination of vesicular stomatitis virus matrix protein gene therapy with low‐dose cisplatin improves therapeutic efficacy against murine melonoma
Author(s) -
Luo Shan,
Chen Ping,
Luo Zichao,
Zhang Ping,
Sun Ping,
Shi Wei,
Li Zhiyong,
Zhang Xiaolong,
Wang Liqiang,
Chen Xin,
Wei Yuquan,
Wen Yanjun
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01507.x
Subject(s) - cisplatin , combination therapy , in vivo , melanoma , genetic enhancement , cancer research , pharmacology , vesicular stomatitis virus , apoptosis , cd8 , medicine , ctl* , immunology , biology , virus , chemotherapy , immune system , gene , biochemistry , microbiology and biotechnology
Vesicular stomatitis virus (VSV) matrix protein (MP) can directly induce apoptosis via the mitochondrial pathway due to the inhibition of host gene expression. Our previous studies have demonstrated that MP gene therapy efficiently suppressed the growth of malignant tumor in vitro and in vivo . The present study was designed to determine the possibility that the combination of MP gene therapy with low‐dose cisplatin would improve therapeutic efficacy against murine melanoma. Immunocompetent C57BL/6 mice bearing B16‐F10 melanoma were established. Mice were treated once every 5 days with i.v. administration of 10 μg pVAX‐MP/30 μg liposome complex per mouse for 16 days and i.p. delivery of cisplatin at 4 mg/kg/mouse on days 6 and 12 after the initiation of MP treatment. We found that MP + cisplatin treatment resulted in significant inhibition of tumor growth and improved the survival time of melanoma‐bearing mice. MP successfully inhibited angiogenesis as assessed by CD31. Histological examination revealed that the combination therapy led to significant increased induction of apoptosis, tumor necrosis, and elevated CD8 + lymphocyte infiltration. Furthermore, the induction efficacy of the CTL response was dramatically enhanced by the combination therapy. Our findings may prove useful in further explorations of the application of these combinational approaches to the treatment of malignant melanoma. ( Cancer Sci 2010; 101: 1219–1225)