Vocational School of Health Services, Bursa Uludag University, Bursa, Turkey.
Department of Biology, Science and Art Faculty, Bursa Uludag University, Bursa, Turkey.
J Cell Biochem. 2023 Aug;124(8):1203-1219. doi: 10.1002/jcb.30442. Epub 2023 Jul 14.
Non-small cell lung cancer (NSCLC) is the most common type of the lung cancer. Despite development in treatment options in NSCLC, the overall survival ratios is still poor due to epithelial and mesenchymal transition (EMT) feature and associated metastasis event. Thereby there is a need to develop strategy to increase antitumor response against the NSCLC cells by targeting EMT pathway with combination drugs. Niclosamide and chalcone complexes are both affect cancer cell signaling pathways and therefore inhibit the EMT pathway. In this study, it was aimed to increase antitumor response and suppress EMT pathway in NSCLC cells by combining niclosamide and chalcone complexes. SRB cell viability assay was performed to investigate the anticancer activity of drugs. The drugs were tested on both NSCLC cells (A549 and H1299) and normal lung bronchial cells (BEAS-2B). Then the two drugs were combined and their effects on cancer cells were evaluated. Fluorescence imaging and enzyme-linked immunosorbent assay were performed on treated cells to observe the cell death manner. Wound healing assay, real-time quantitative polymerase chain reaction, and western blot analysis were performed to measure EMT pathway activity. Our results showed that niclosamide and chalcone complexes combination kill cancer cells more than normal lung bronchial cells. Compared to single drug administration, the combination of both drugs killed NSCLC cells more effectively by increasing apoptotic activity. In addition, the combination of niclosamide and chalcone complexes decreased multidrug resistance and EMT activity by lowering their gene expressions and protein levels. These results showed that niclosamide and chalcone complexes combination could be a new drug combination for the treatment of NSCLC.
非小细胞肺癌（NSCLC）是肺癌中最常见的类型。尽管 NSCLC 的治疗选择有所发展，但由于上皮间质转化（EMT）特征和相关转移事件，总体生存率仍然较差。因此，需要开发一种通过靶向 EMT 途径与联合药物增加针对 NSCLC 细胞的抗肿瘤反应的策略。尼氯硝唑和查尔酮复合物都可以影响癌细胞信号通路，因此可以抑制 EMT 途径。在这项研究中，旨在通过联合使用尼氯硝唑和查尔酮复合物来提高 NSCLC 细胞的抗肿瘤反应并抑制 EMT 途径。通过 SRB 细胞活力测定法来研究药物的抗癌活性。在非小细胞肺癌细胞（A549 和 H1299）和正常肺支气管细胞（BEAS-2B）上测试了这些药物。然后将两种药物联合使用，并评估它们对癌细胞的影响。对处理过的细胞进行荧光成像和酶联免疫吸附测定，以观察细胞死亡方式。进行划痕愈合试验、实时定量聚合酶链反应和 Western blot 分析，以测量 EMT 途径活性。我们的结果表明，尼氯硝唑和查尔酮复合物联合使用比正常肺支气管细胞更能杀死癌细胞。与单一药物给药相比，两种药物的联合使用通过增加细胞凋亡活性更有效地杀死 NSCLC 细胞。此外，尼氯硝唑和查尔酮复合物的联合使用通过降低其基因表达和蛋白水平降低了多药耐药性和 EMT 活性。这些结果表明，尼氯硝唑和查尔酮复合物联合使用可能成为治疗 NSCLC 的一种新的药物联合方案。
