Effect and Mechanism of Fuzheng Oral Liquid on Anlotinib Resistance in Non-Small Cell Lung Cancer Cells

Abstract

To explore the reversal effect of Fuzheng oral liquid on anlotinib resistance in non-small cell lung cancer cells and its mechanism is the objective of the study. 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay and flow cytometric assay were performed to evaluate the effects of anlotinib on the proliferation and apoptotic cycles of adenocarcinomic human alveolar basal epithelial cell line A549 cells, respectively. Western blot was performed to detect the expression levels of unfolded protein response, endoplasmic reticulum-associated degradation, E-cadherin, vimentin, beta-catenin, transcription factor 4 and Axin in anlotinib-resistant cell line A549/AL3818 cells. Anlotinib-resistant A549 cells were successfully constructed and named as A549/AL3818. Fuzheng oral solution had proliferation inhibition, apoptosis induction and cycle blocking effects on A549/AL3818 cells. High dose of Fuzheng oral liquid was able to inhibit unfolded protein response and endoplasmic reticulum-associated degradation, expression in A549/ AL3818 cells and suppress wingless-related integration signaling pathway and epithelial-mesenchymal transition progression in A549/AL3818 cells. The inhibitory effect of Fuzheng oral liquid on winglessrelated integration signaling pathway and epithelial-mesenchymal transition progression was the same as that of paired box protein 6. Fuzheng oral liquid inhibited epithelial-mesenchymal transition progression through regulating unfolded protein response-endoplasmic reticulum-associated degradation signaling pathway, thereby reversing the resistance of non-small cell lung cancer cells to anlotinib.