Department of Pharmacology, United Medical and Dental College, Karachi, Pakistan.
Department of Physiology, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.
Pak J Pharm Sci. 2023 Mar;36(2):501-506.
Lung cancer is the most typical form of cancer that results in death worldwide. Patients with non-small cell lung cancer (NSCLC) have an around 15% survival rate despite of advancement in cancer treatment. This study aimed to evaluate the combined effect of celecoxib and bevacizumab on NSCLC using A549 cells as an in vitro model. The A549 cells were culture and treated with celecoxib, bevacizumab and their combination and the cell proliferation was assessed using MTT assay, whereas cell apoptosis was analyzed using flowcytometry. The effects on the apoptotic genes were examined using western blotting, while qPCR was used for analyzing the VEGF and MMP-9 expression. Celecoxib, bevacizumab and their combination exhibited a dose dependent inhibition (p<0.001). The rate of apoptosis was 14.1% and 26.5% but when the two drugs were combined, the rate of apoptosis was significantly increased due to synergism by 52.2% (p<0.001). Western blotting displayed that co-treatment significantly up regulated proapoptotic genes (caspase-3 and -9) and down regulated anti-apoptotic gene (Bcl-2) (p<0.001). Additionally, VEGF and MMP-9 expression were both significantly reduced with co-treatment compared to the control (p<0.001). Celecoxib combined with bevacizumab synergistically inhibited NSCLC by inducing apoptosis and modulating VEGF and MMP-9 expression.
肺癌是全球导致死亡的最典型癌症形式。尽管癌症治疗取得了进展,非小细胞肺癌(NSCLC)患者的生存率仍约为 15%。本研究旨在使用 A549 细胞作为体外模型,评估塞来昔布和贝伐珠单抗联合对 NSCLC 的治疗效果。将 A549 细胞培养并分别用塞来昔布、贝伐珠单抗和联合用药处理,通过 MTT 检测评估细胞增殖,通过流式细胞术分析细胞凋亡。采用 Western blot 检测凋亡基因的变化,qPCR 检测 VEGF 和 MMP-9 的表达。塞来昔布、贝伐珠单抗及其联合用药均呈剂量依赖性抑制(p<0.001)。细胞凋亡率分别为 14.1%和 26.5%,但当两种药物联合使用时,由于协同作用,细胞凋亡率显著增加了 52.2%(p<0.001)。Western blot 显示,联合用药显著上调促凋亡基因(caspase-3 和 -9),下调抗凋亡基因(Bcl-2)(p<0.001)。此外,与对照组相比,联合用药时 VEGF 和 MMP-9 的表达均显著降低(p<0.001)。塞来昔布联合贝伐珠单抗通过诱导细胞凋亡和调节 VEGF 和 MMP-9 的表达,协同抑制 NSCLC。