FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced a
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RESEARCH ARTICLE
Open Access
FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis Wei Gao1, Jinxiao Liang2, Yiru Ye1, Jinlan Lu1, Tongtong Lin1, Na Wang1, Jingyin Dong1 and Jianping Pan1*
Abstract Background: Increased fucosylation is associated with the chemoresistance phenotype. Meanwhile, fucosyltransferase IV (FUT4) amounts are frequently elevated in lung cancer and may be related to increased chemoresistance. Methods: In the present work, FUT4’s role in cisplatin-induced apoptosis was assessed in A549 and H1975 cells, respectively. To clarify whether the FUT4 gene attenuates chemosensitivity in tumor cells, we constructed FUT4siRNA and evaluated its effects on cisplatin-induced apoptosis and cell growth inhibition. Cell viability, apoptosis, migration and invasion assay were conducted to investigate cisplatin sensitivity. The activation of EGFR/ AKT/FOXO1 signaling were measured by western blot. The translocation of FOXO1 was assessed by IFC using Laser Scanning Confocal Microscope. Results: We found that FUT4 knockdown dose-dependently increased cisplatin-associated cytotoxicity. Furthermore, FUT4 silencing induced apoptosis and inhibited proliferation in A549 and H1975 cells by suppressing Akt and FOXO1 phosphorylation induced by cisplatin administration, which resulted in nuclear translocation of FOXO1. Conclusion: These results suggested FUT4 might control chemoresistance to cisplatin in lung cancer by suppressing FOXO1-induced apoptosis. Keywords: FUT4, Chemosensitivity, Cisplatin, NSCLC, FOXO1
Background As one of the main causes of mortality around the world [1], non-small cell lung cancer (NSCLC) contributes to approximately 85% of cancer-related deaths [2] and has limited treatment options [3]. Chemotherapeutics are commonly employed to treat advanced NSCLC. Cisplatin, a platinum drug, kills malignant cells and is widely applied in NSCLC [4]. However, drug resistance * Correspondence: [email protected] 1 Department of Clinical Medicine, Zhejiang University City College School of Medicine, 50 Huzhou Road, Hangzhou 310015, P.R. China Full list of author information is available at the end of the article
constitutes an important clinical challenge, hampering the application in platinum-based chemotherapy of NSCLC [5]. Therefore, deciphering the molecular mechanisms related to chemoresistance would help develop novel strategies for identifying new drug sensitizers that increase the potency of platinum drugs. Cell-surface glycans play important roles in many physiological and pathological processes [6]. Fucose contributes to the structural composition of various carbohydrate chains. The binding of a fucosyl residue to the terminus of glycosidic chains serves as an important component of the carbohydrate structure of some
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium o
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