Vesicular stomatitis virus matrix protein gene enhances the antitumor effects of radiation via induction of apoptosis

Springer Science and Business Media LLC - Tập 13 - Trang 1205-1214 - 2008
Xiao-Bo Du1,2, Jin-Yi Lang3, Jian-Rong XU4, You Lu1, Yan-Jun Wen1, Ju-Mei Zhao1,5, Peng Diao1,3, Zhi-Ping Yuan1, Bin Yao1,2, Ling-Yu Fan1, Guo-Qing Wang1, Li Liu1,3, Zhen-Yu Ding1, Yong-Sheng Wang1, Tao Li3, Rui Wang1, Yun-Qiu Mao1, Bin Kan1, Hong-Bin Wu1, Hong-Xia Li1, Han-Suo Yang1, Hong-Bo Wu1, Yu-Quan Wei1, Xia Zhao1
1National Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
2Department of Oncology, MianYang Central Hospital, MianYang, People’s Republic of China
3Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, People’s Republic of China
4National Key Laboratory of Biotherapy and Cancer Center, School of Life Sciences, Sichuan University, Chengdu, People’s Republic of China
5Department of Pharmacology, Yan’an Medical College, Suide, People’s Republic of China

Tóm tắt

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.

Tài liệu tham khảo

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