Translational cancer research · 2025
A novel pyridazinone and thiophene compound IMB5043 activated apoptosis and autophagy in cisplatin-resistant non-small cell lung cancer cells.
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Hou Yingzheng, Cao Xueting, Cao Rui, Tang Hongmei, Chen Jing
Аннотация
BACKGROUND: Lung cancer is still one of the top three malignant tumors in the world at present and one of the cancers with the lowest survival rate. Cisplatin is one of the most commonly used chemotherapy drugs, but the development of drug resistance can lead to the death of patients who are ineffective to the treatment. IMB5043 is a pyridazinone and thiophene compound which is cytotoxic to cancer cells. This article aims to explore its effect on cisplatin-resistant lung cancer cells.
METHODS: Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to detect the cyto-toxicity of different concentrations of cisplatin and IMB5043 on non-small cell lung cancer (NSCLC) H460 cells and its cisplatin-resistant cell (H460/DDP). The effect of IMB5043 on cell migration and invasion and its molecular mechanism were studied by scratch experiment, transwell experiment and Western blot. Hoechst 33342 staining, acridine orange/ethidium bromide (AO/EB) double fluorescence staining and Western blot were used to detect whether IMB5043 induced cell apoptosis and explore its molecular mechanism. Acridine orange (AO) staining and Western blotting were used to detect whether IMB5043 induced autophagy in cells.
RESULTS: IMB5043 induced the death of cisplatin-resistant NSCLC cells by activating apoptosis and autophagy, and inhibited the epithelial-mesenchymal transition (EMT) pathway to reduce cell migration and invasion.
CONCLUSIONS: IMB5043 is an effective pyridazinone and thiophene derivatives with antitumor effects and may be suitable for cisplatin-based combination therapy in a subset of patients with cisplatin-resistant NSCLC.
METHODS: Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to detect the cyto-toxicity of different concentrations of cisplatin and IMB5043 on non-small cell lung cancer (NSCLC) H460 cells and its cisplatin-resistant cell (H460/DDP). The effect of IMB5043 on cell migration and invasion and its molecular mechanism were studied by scratch experiment, transwell experiment and Western blot. Hoechst 33342 staining, acridine orange/ethidium bromide (AO/EB) double fluorescence staining and Western blot were used to detect whether IMB5043 induced cell apoptosis and explore its molecular mechanism. Acridine orange (AO) staining and Western blotting were used to detect whether IMB5043 induced autophagy in cells.
RESULTS: IMB5043 induced the death of cisplatin-resistant NSCLC cells by activating apoptosis and autophagy, and inhibited the epithelial-mesenchymal transition (EMT) pathway to reduce cell migration and invasion.
CONCLUSIONS: IMB5043 is an effective pyridazinone and thiophene derivatives with antitumor effects and may be suitable for cisplatin-based combination therapy in a subset of patients with cisplatin-resistant NSCLC.