Physapubescin B enhances the sensitivity of gastric cancer cells to trametinib by inhibiting the STAT3 signaling pathway.

In this study, trametinib, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, reduced the p-ERK level and significantly increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in GC cells, resulting in reduced sensitivity to trametinib. Physapubescin B (PB), a steroidal compound extracted from the plant Physalis pubescens L., inhibited the proliferation and induced the apoptosis of GC cells by suppressing STAT3 phosphorylation. The combination of PB and trametinib suppressed the STAT3 phosphorylation induced by trametinib, and synergistically suppressed gastric tumor growth in vitro and in vivo. Together, these results indicate that inhibition of both MEK and STAT3 may be effective for patients with MAPK/ERK pathway-addicted GC.
PMID: 33035574 [PubMed - as supplied by publisher]

Source: Toxicology and Applied Pharmacology - October 6, 2020 Category: Toxicology Authors: Dai C, Shen L, Jin W, Lv B, Liu P, Wang X, Yin Y, Fu Y, Liang L, Ma Z, Zhang X, Wang Y, Xu D, Chen Z Tags: Toxicol Appl Pharmacol Source Type: research