Abstract:

Objective   To explore the effects of erlotinib combined with celecoxib on the tumor growth and angiogenesis of lung cancer xenografts in nude mice. Methods   Human lung cancer cell A549 was subcutaneously injected to establish the nude mice xenograft model. The nude mice with tumor were randomly divided into four groups：the control group, the celecoxib group, the erlotinib group and the combined group.  All the mice were given the gavage administration. The status of the mice were observed everyday , and the volume of the tumor was measured twice a week to obtain the tumor growth curve. The mice were put to death to collect the tumor tissues after 40 days. The microvessel density (MVD) was detected by the immunohistochemistry analyses and the expressions of Bcl-2 and Bax were detected by Western Blotting. Blood samples were collected to detect the sVEGF level by ELISA. Results   The tumor volumes of the combined group were significantly smaller compared with the control group, the celecoxib group and the erlotinib group（P＜0.05）. The microvessel density and the sVEGF level of the combined group were decreased compared with the control group, the celecoxib group and the erlotinib group（P＜0.05）. The Bcl-2 level of the erlotinib group was lower compared with the control group. There was no significant difference of the Bcl-2 level between the celecoxib group and the control group (P>0.05). The Bcl-2 level of the combined group is lower compared with the control group, the celecoxib group and the erlotinib group（P＜0.05）. There was no significant difference of the Bax level among the control group, the celecoxib group and the combined group(P>0.05). The value of Bcl-2/Bax of the combined group was lower compared with the celecoxib group and the erlotinib group（P＜0.05）. Conclusion   Erlotinib combined with celecoxib  have more effective growth inhibition on the human lung cancer xenograft model than erlotinib or celecoxib separately. The possible mechanism may be related to the decrease of  microvessels and the increase of  tumor apoptosis.

Key words: Lung adenocarcinoma; Erlotinib; Celecoxib; Xenograft model Angiogenesis of tumor