title: Avastin® in combination with gemcitabine and cisplatin significantly inhibits tumor angiogenesis and increases the survival rate of human A549 tumor-bearing mice.
abstract: The aim of this study was to investigate the effect of Avastin® in combination with gemcitabine and cisplatin (GP) on the tumor growth of A549 tumor-bearing mice and the potential anti-tumor mechanism. A total of 30 human A549 tumor-bearing nude mice were randomly divided into the Avastin, chemotherapy and combined treatment groups for treatment with an intraperitoneal injection of Avastin (5 mg/kg) (Avastin group); an intraperitoneal injection of gemcitabine (4 mg/kg) and cisplatin (4 mg/kg) (chemotherapy group); or intraperitoneal injections of Avastin and GP (combined treatment group). The mice were observed for 30 days and the tumor growth, survival and body weight of the mice in the three groups were analyzed. The protein level of vascular endothelial growth factor (VEGF) in the tumor tissues was analyzed by ELISA. The vascular density and structural changes of the tumor were analyzed using immunohistochemistry. Compared with the Avastin and chemotherapy groups, the tumor growth of mice in the combined treatment group was significantly inhibited, and the survival rate of the mice was increased significantly. No difference in body weight was observed among the three groups of mice (P>0.05). The levels of VEGF in the combined treatment group tumor tissues were significantly reduced compared with those in the chemotherapy group tumor tissues (P<0.05). Furthermore, the vessel density of the tumor tissue in the combined treatment group was significantly reduced compared with that in the chemotherapy group (P<0.05), and the number of normal vessels in the combined treatment group tumors was significantly higher than that in the chemotherapy group tumors after 7 days of treatment (P<0.05). In conclusion, Avastin can significantly decrease the level of VEGF in tumor tissue, inhibit tumor angiogenesis and promote the normalization of tumor vascular structure, which may explain the enhanced efficacy of Avastin in combination with chemotherapy.
authors.affiliation: Department of Intensive Care Unit, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors.forename: Xizheng
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Intensive Care Unit, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors.forename: Mingkai
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Intensive Care Unit, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
keywords: Avastin®; cisplatin; combined therapy; gemcitabine; tumor vessel