Ad-endostatin treatment combined with low-dose irradiation in a murine lung cancer model

Li,Xiao-Peng; Zhang,Hai-Long; Wang,Hui-Juan; Li,Yong-Xia; Li,Meng; Lu,Lian; Wan,Yang; Zhou,Bai-Ling; Liu,Yan; Pan,Ying; Wu,Xiao-Zhe; Fan,Ying-Zi; Yu,Chao-Heng; Wei,Yu-Quan; Shi,Hua-Shan

doi:10.3892/or.2014.3253

Ad-endostatin treatment combined with low-dose irradiation in a murine lung cancer model

Authors:
- Xiao-Peng Li
- Hai-Long Zhang
- Hui-Juan Wang
- Yong-Xia Li
- Meng Li
- Lian Lu
- Yang Wan
- Bai-Ling Zhou
- Yan Liu
- Ying Pan
- Xiao-Zhe Wu
- Ying-Zi Fan
- Chao-Heng Yu
- Yu-Quan Wei
- Hua-Shan Shi
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Affiliations: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: June 12, 2014 https://doi.org/10.3892/or.2014.3253
Pages: 650-658

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Abstract

Radiation therapy is a conventional strategy for treating advanced lung cancer yet is accompanied by serious side-effects. Its combination with other strategies, such as antiangiogenesis and gene therapy, has shown excellent prospects. As one of the potent endogenous vascular inhibitors, endostatin has been widely used in the antiangiogenic gene therapy of tumors. In the present study, LL/2 cells were infected with a recombinant adenovirus encoding endostatin (Ad-endostatin) to express endostatin. The results showed that LL/2 cells infected with the Ad-endostatin efficiently and longlastingly expressed endostatin. In order to further explore the role of Ad-endostatin combined with irradiation in the treatment of cancer, a murine lung cancer model was established and treated with Ad-endostatin combined with low-dose irradiation. The results showed that the combination treatment markedly inhibited tumor growth and metastasis, and prolonged the survival time of the tumor-bearing mice. Furthermore, this significant antitumor activity was associated with lower levels of microvessel density and anoxia factors in the Ad-Endo combined with irradiation group, and with an increased apoptotic index of tumor cells. In addition, no serious side-effects were noted in the combination group. Based on our findings, Ad-endostatin combined with low-dose irradiation may be a rational alternative treatment for lung cancer and other solid tumors.

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