title: Ad-endostatin treatment combined with low-dose irradiation in a murine lung cancer model.
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.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yong-Xia
authors.initials: YX
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lian
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Bai-Ling
authors.initials: BL
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xiao-Zhe
authors.initials: XZ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Chao-Heng
authors.initials: CH
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hua-Shan
authors.initials: HS
authors.lastname: Shi
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods*; D000229:Dependovirus / Q000235:genetics; D043169:Endostatins / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009362:Neoplasm Metastasis / Q000628:therapy; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D043169:Endostatins