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. 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. 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. These results suggested FUT4 might control chemoresistance to cisplatin in lung cancer by suppressing FOXO1-induced apoptosis.

中文翻译：

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FUT4siRNA通过激活FOXO1诱导的细胞凋亡增强非小细胞肺癌对顺铂的化学敏感性。

岩藻糖基化增加与化学抗性表型有关。同时，岩藻糖基转移酶IV（FUT4）的量在肺癌中经常升高，并且可能与化学抗性增加有关。在目前的工作中，分别在A549和H1975细胞中评估了FUT4在顺铂诱导的细胞凋亡中的作用。为了阐明FUT4基因是否减弱肿瘤细胞的化学敏感性，我们构建了FUT4siRNA并评估了其对顺铂诱导的细胞凋亡和细胞生长抑制的影响。进行细胞活力，凋亡，迁移和侵袭试验以研究顺铂敏感性。通过蛋白质印迹法检测EGFR / AKT / FOXO1信号的激活。通过IFC使用激光扫描共聚焦显微镜评估FOXO1的易位。我们发现FUT4组合式剂量依赖性地增加了顺铂相关的细胞毒性。此外，FUT4沉默通过抑制顺铂给药诱导的Akt和FOXO1磷酸化而诱导A549和H1975细胞凋亡并抑制A549和H1975细胞的增殖，从而导致FOXO1的核易位。这些结果表明FUT4可能通过抑制FOXO1诱导的细胞凋亡来控制肺癌对顺铂的化学耐药性。