Xia Honggang, Ye Jianfei, Bai Hongyu, Wang Changli
Graduate School of Tianjin Medical University, Tianjin 300070, China;Department of Thoracic Surgery, Tianjin Dagang Oil Field General Hospital, Tianjin 300280, China.
Zhongguo Fei Ai Za Zhi. 2013 Dec;16(12):625-31. doi: 10.3779/j.issn.1009-3419.2013.12.02.
Neoadjuvant chemotherapy is a new development in the treatment of lung cancer. In recent years, cetuximab and celecoxib have been commonly used in this procedure. This study aims to explore the effect of cetuximab combined with celecoxib on apoptosis and KDR and AQP1 expression in lung cancer A549 cells.
The cells were cultured in RPMI-1640 and then divided into four groups: control group, 1 nmol/L cetuximab group, 25 µmol/L celecoxib group, and 1 nmol/L cetuximab+25 µmol/L celecoxib group. The treatment time was 48 h. The mRNA and protein expression levels of KDR and AQP1 were detected by RT-PCR and Western blot, respectively. The apoptosis, proliferation, and invasive ability of A549 cells before and after transfection were examined using flow cytometry, MTT, and transwell methods.
Cetuximab and celecoxib inhibited the growth of A549 cells in a dose-dependent manner. Their combination produced a greater growth inhibition than when either was used alone (P<0.01). Cetuximab and celecoxib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P<0.01). Cetuximab in combination with celecoxib also induced G1 phase arrest and downregulated the expression of KDR and AQP1 in A549 cells (P<0.05). As a result, the invasion ability of the A549 cells was significantly decreased.
Cetuximab in combination with celecoxib can synergistically inhibit the growth of A549 cells and downregulate the expression of KDR and AQP1 in A549 cells. The combination of cetuximab and celecoxib is a potential strategy for lung cancer therapy.
新辅助化疗是肺癌治疗的一项新进展。近年来，西妥昔单抗和塞来昔布已普遍应用于该治疗过程。本研究旨在探讨西妥昔单抗联合塞来昔布对肺癌A549细胞凋亡以及KDR和水通道蛋白1（AQP1）表达的影响。
将细胞培养于RPMI - 1640培养基中，然后分为四组：对照组、1 nmol/L西妥昔单抗组、25 μmol/L塞来昔布组和1 nmol/L西妥昔单抗 + 25 μmol/L塞来昔布组。处理时间为48小时。分别采用逆转录 - 聚合酶链反应（RT - PCR）和蛋白质免疫印迹法检测KDR和AQP1的mRNA和蛋白表达水平。使用流式细胞术、MTT法和Transwell法检测转染前后A549细胞的凋亡、增殖和侵袭能力。
西妥昔单抗和塞来昔布均以剂量依赖方式抑制A549细胞生长。它们联合使用时产生的生长抑制作用比单独使用任一药物时更强（P < 0.01）。西妥昔单抗和塞来昔布均诱导A549细胞凋亡，联合使用时凋亡率更高（P < 0.01）。西妥昔单抗联合塞来昔布还诱导A549细胞G1期阻滞，并下调A549细胞中KDR和AQP1的表达（P < 0.05）。结果，A549细胞的侵袭能力显著降低。
西妥昔单抗联合塞来昔布可协同抑制A549细胞生长，并下调A549细胞中KDR和AQP1的表达。西妥昔单抗与塞来昔布联合是一种潜在的肺癌治疗策略。
