PMID: 32509166Jun 9, 2020Paper

Astragalus polysaccharides reverse gefitinib resistance by inhibiting mesenchymal transformation in lung adenocarcinoma cells

American Journal of Translational Research
Jia WeiJing Yu

Abstract

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been used as first-line recommended therapy for EGFR mutant non-small cell lung cancer patients. However, epithelial-mesenchymal transition (EMT) can reduce EGFR-TKI sensitivity and lead to resistance. This study was designed to investigate the reversal effect of astragalus polysaccharides (APS) on gefitinib resistance (GR) and to elucidate the underlying mechanisms. PC9 and HCC827 lung cancer cells were stimulated by TGF-β1 to develop EMT-associated GR cells. Cell proliferation, migration and apoptosis assays were used to confirm the effect of gefitinib on GR cells and the therapeutic effect of APS on GR cells after knockdown and over-expression of related signaling pathways. Reverse transcription polymerase chain reaction, western blotting, and immunofluorescent staining assays were used to evaluate the expression levels of E-cadherin, N-cadherin, vimentin, PD-L1, and SREBP-1. Furthermore, proliferation and migration abilities were enhanced, while apoptosis ability was weakened in EMT-associated GR cells. After over-expression of PD-L1, expression levels of N-cadherin, vimentin and SREBP-1 increased, while expression of E-cadherin decreased. After kn...Continue Reading

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