Vesicular stomatitis virus matrix protein gene enhances the antitumor effects of radiation via induction of apoptosis.
Vesicular stomatitis virus (VSV) matrix (M) protein can directly induce apoptosis by inhibiting host gene expression when it is expressed in the absence of other viral components. Previously, we found that the M protein gene complexed to DOTAP-cholesterol liposome (Lip-MP) can suppress malignant tumor growth in vitro and in vivo; however, little is known regarding the biological effect of Lip-MP combined with radiation. The present study was designed to determine whether Lip-MP could enhance the antitumor activity of radiation. LLC cells treated with a combination of Lip-MP and radiation displayed apparently increased apoptosis compared with those treated with Lip-MP or radiation alone. Mice bearing LLC or Meth A tumors were treated with intratumoral or intravenous injections of Lip-MP and radiation. The combined treatment significantly reduced mean tumor volumes compared with either treatment alone in both tumor models and prolonged the survival time in Meth A tumor models and the intravenous injection group of LLC tumor models. Moreover, the antitumor effects of Lip-MP combined with radiation were greater than their additive effects when compared with the expected effects of the combined treatment in vivo. This study suggests that Lip-MP enhanced the antitumor activity of radiation by increasing the induction of apoptosis.
Du
Xiao-Bo
XB
National Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
Lang
Jin-Yi
JY
Xu
Jian-Rong
JR
Lu
You
Y
Wen
Yan-Jun
YJ
Zhao
Ju-Mei
JM
Diao
Peng
P
Yuan
Zhi-Ping
ZP
Yao
Bin
B
Fan
Ling-Yu
LY
Wang
Guo-Qing
GQ
Liu
Li
L
Ding
Zhen-Yu
ZY
Wang
Yong-Sheng
YS
Li
Tao
T
Wang
Rui
R
Mao
Yun-Qiu
YQ
Kan
Bin
B
Wu
Hong-Bin
HB
Li
Hong-Xia
HX
Yang
Han-Suo
HS
Wu
Hong-Bo
HB
Wei
Yu-Quan
YQ
Zhao
Xia
X
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005720:Gamma Rays; D015316:Genetic Therapy; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000627:therapeutic use*
D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; C094460:M protein, Vesicular stomatitis virus; D000644:Quaternary Ammonium Compounds; D014763:Viral Matrix Proteins; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane