Open AccessResveratrol reduces drug resistance of SCLC cells by suppressing the inflammatory microenvironment and the STAT3/VEGF pathway
Author(s) -
Hou Cong,
Lu Lijun,
Liu Zhanye,
Lian Yingjie,
Xiao Jianguang
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13230
Subject(s) - stat3 , resveratrol , cancer research , stat protein , drug resistance , vascular endothelial growth factor , chemistry , pharmacology , biology , signal transduction , microbiology and biotechnology , vegf receptors
DNA‐damaging agents, such as doxorubicin (Adriamycin), are widely used for the treatment of small cell lung cancer (SCLC). However, drug resistance is one of the major challenges for treatment of SCLC. Herein, we investigated the mechanisms underlying drug resistance in SCLC cells and the effects of resveratrol (Res) on drug resistance. We report that Adriamycin treatment of H69AR (multidrug resistance phenotype) cells resulted in a lower rate of growth inhibition, up‐regulation of MRP1 and P‐glycoprotein (P‐gp), and higher P‐gp activity as compared with susceptible H69 cells treated with Adriamycin. Moreover, the signal transducer and activator of transcription 3/vascular endothelial growth factor (STAT3/VEGF) pathway was overactivated in H69AR cells, especially after interleukin‐23 treatment. The inflammatory microenvironment promoted the drug resistance of H69AR cells by activating the STAT3/VEGF pathway. The addition of Res suppressed the expression levels of inflammatory mediators, inhibited the STAT3/VEGF pathway, impeded P‐gp activity, and decreased the drug resistance of H69AR cells. H69AR cells exhibited Adriamycin resistance through activation of the STAT3/VEGF pathway, and Res ameliorated the inflammatory microenvironment to suppress the STAT3/VEGF pathway to reduce drug resistance. Our results suggest that Res may have therapeutic potential for SCLC treatment.