β-carboline compound-10830733 suppresses the progression of non-small cell lung cancer by inhibiting the PI3K/Akt/GSK 3β signaling pathway.

Abstract

Lung cancer is one of the most commonly diagnosed cancers worldwide, with non-small cell lung cancer (NSCLC) accounting for 80-85% of cases. To clarify the mechanisms underlying its onset and development, and to identify small molecule compounds that target related pathways effectively inhibiting tumor development and transformation. Small molecular compounds with a β-carboline nucleus exhibit a range of biological activities, with significant anti-tumor effects. A series of small molecule β-carboline compounds were synthesized and the dominant structure 1- (3-chlorophenyl) - 9H -pyridino - [3,4-b] indole - 3 -carboxylic acid methyl ester (10830733) was initially screened out. However, the effect of 10830733 on NSCLC is unclear. In this study, we investigated the anti-NSCLC activity of 10830733 and explored its potential mechanisms of action. First, we found that 10830733 decreased proliferation and invasion and promoted apoptosis, as well as S and G2 phase cell cycle arrest in NSCLC cells. Furthermore, network pharmacological analysis and Western blot confirmed that 10830733 inhibits the PI3K/Akt/GSK 3β pathway, and that the PI3K inhibitor LY294002 enhances the effects of 10830733 on proliferation, invasion, apoptosis, S and G2 phase arrest, and the expression of PI3K/Akt/GSK 3β related proteins. In conclusion, our data demonstrate that 10830733 reduces proliferation and invasion, promotes S and G2 phase arrest and apoptotic cell death in NSCLC cells by suppressing the PI3K/Akt/GSK 3β signaling pathway, suggesting that 10830733 could be a promising new candidate for NSCLC therapy.