PEITC restores chemosensitivity in cisplatin-resistant non-small cell lung cancer by targeting c-Myc/miR-424-5p

This is the authors' abstract. We don't add key points for this paper.

We aimed to investigate the potential of phenethyl isothiocyanate (PEITC) as an effective therapeutic agent in overcoming cisplatin resistance in non-small cell lung cancer (NSCLC). Cell viability was measured using the CCK-8 assay and flow cytometry, and a xenograft model was established to verify the antitumor effect of PEITC on A549/DDP cells. The JASPAR database was used to predict the potential molecular mechanisms. Mechanistic exploration was conducted using Western blot and qRT-PCR analyses, and predictions were validated with a dual-luciferase reporter assay. The findings show that PEITC treatment led to decreased cell proliferation, increased apoptosis, and cessation of cell cycle progression at G1 phase. PEITC inhibited tumor growth in a concentration-dependent manner in a mouse xenograft model. Examination of the possible mechanism of PEITC showed that this compound led to down-regulation of miR-424-5p and c-Myc, up-regulation of suppressor of cytokine signaling 5/6 (SOCS5/6), and down-regulation of AKT/PI3K/mTOR signaling. A dual-luciferase reporter assay showed that miR-424-5p targeted c-Myc, and that silencing of c-Myc decreased the expression of downstream genes. These results suggest that PEITC inhibited the growth and increased the sensitivity of cisplatin-resistant NSCLC cells by targeting c-Myc and down-regulating the PI3K/AKT/mTOR pathway. Clinical trial number: not applicable.