Available online 22 November 2022, 104777

Propofol reduces Cis resistance of NSCLC cells.

Propofol induces GPX4-mediated ferroptosis.

miR-744-5p/miR-615-3p inhibits GPX4 transcription.

miR-744-5p/miR-615-3p downregulation attenuates the role of propofol.

Propofol limits Cis-treated tumor growth via the miR-744-5p/miR-615-3p/GPX4 axis.

Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Propofol functions as a tumor-inhibitor drug by regulating microRNAs (miRNAs). The primary objective of this study is to explore the functional mechanism of propofol in cisplatin (Cis) resistance of NSCLC cells by regulating the miR-744-5p/miR-615-3p axis. Cis-resistant NSCLC cell lines were cultured and chemotherapy-resistance (CR) to Cis of NSCLC cells to Cis was confirmed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, flow cytometry, and colony formation assay. Ferroptosis was evaluated by measurement of iron content, ferroptosis-related proteins (GPX4/ ACSL4/SLC7A11) and lipid peroxidation (SOD/GSH/MDA) through Western blot analysis and assay kits. . After the dual-luciferase reporter assay to testify gene interactions, the functional rescue experiments and nude mouse tumor formation assay were performed. Based on results, propofol reduced IC50 value and CR of NSCLC cells to Cis and induced ferroptosis. Propofol upregulated miR-744-5p/miR-615-3p to inhibit GPX4 transcription. Upregulation of GPX4 or downregulation of miR-744-5p/miR-615-3p attenuated the inhibitory effect of propofol on CR to Cis. In vivo, propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis. In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of NSCLC cells to Cis through the miR-744-5p/miR-615-3p axis.

To study the effect of propofol on chemoresistance of non-small cell lung cancer (NSCLC), and to provide a new theoretical basis for the treatment of NSCLC.

Cisplatin

Chemotherapy-resistance

Ferroptosis

Non-small cell lung cancer

Propofol

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