研究动态
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Celecoxib和bevacizumab通过诱导凋亡和调节VEGF和MMP-9表达,协同抑制非小细胞肺癌。

Celecoxib and bevacizumab synergistically inhibit non-small cell lung cancer by inducing apoptosis and modulating VEGF and MMP-9 expression.

发表日期:2023 Mar
作者: Abdul Qadir, Zurqa Khalid, Fareha Kashan Theba, Muhammad Mujtaba Ali, Mahayrookh Asif, Fatima Rizvi
来源: Cell Death & Disease

摘要:

肺癌是全球导致死亡的最常见的癌症类型。尽管癌症治疗取得了进展,但非小细胞肺癌(NSCLC)患者的存活率仅约为15%。本研究旨在使用A549细胞作为离体模型评估Celecoxib和bevacizumab的联合作用对NSCLC的影响。将A549细胞培养并分别用Celecoxib、bevacizumab及其组合进行处理,使用MTT法评估细胞增殖,使用流式细胞术分析细胞凋亡。通过Western blotting检测凋亡相关基因,通过qPCR分析VEGF和MMP-9的表达。Celecoxib、bevacizumab及其组合剂显示剂量依赖性的抑制(p<0.001)。当两种药物合并使用时,凋亡率从14.1%和26.5%显著增加至52.2%,具有协同作用(p<0.001)。Western blotting显示联合处理显著上调损伤基因(caspase-3和-9)的表达,并下调抗凋亡基因(Bcl-2)的表达(p<0.001)。此外,与对照相比,联合处理明显降低了VEGF和MMP-9的表达(p<0.001)。Celecoxib与bevacizumab联合抑制了NSCLC,通过诱导凋亡和调控VEGF和MMP-9的表达实现。
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.