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D-allo 果糖与顺铂联用对非小细胞肺癌细胞的增效抗肿瘤作用。

Additive antitumour effect of D‑allose in combination with cisplatin in non-small cell lung cancer cells.

机构信息

Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.

Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.

出版信息

Oncol Rep. 2018 Mar;39(3):1292-1298. doi: 10.3892/or.2018.6192. Epub 2018 Jan 4.

Abstract

D‑allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D‑allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D‑allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC‑LCD; adenocarcinomas: A549, HI1017, RERF‑LC‑A1 and NCI-H1975) were treated with D‑allose (50 mM) with or without cisplatin (5 µM). D‑allose inhibited cell growth, particularly in EBC1 and VMRC‑LCD cells. In combination with cisplatin, D‑allose had a synergistic growth inhibitory effect. D‑allose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D‑allose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice. After tumourigenesis, D‑allose and cisplatin were injected. In this mouse xenograft model, additional treatment with D‑allose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki‑67 and higher TXNIP expression. In conclusion, D‑allose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, D‑allose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in D‑allose-mediated antitumour effects in NSCLC.

摘要

D-allo 是一种稀有糖,已被证明对多种恶性肿瘤具有生长抑制作用。然而,D-allo 对肺癌进展的影响尚未被研究过。为了研究 D-allo 在肺癌细胞中的抗肿瘤作用及其机制,用 D-allo(50mM)处理人非小细胞肺癌(NSCLC)细胞系(鳞状细胞癌:EBC1 和 VMRC-LCD;腺癌:A549、HI1017、RERF-LC-A1 和 NCI-H1975),有或没有顺铂(5μM)。D-allo 抑制细胞生长,特别是在 EBC1 和 VMRC-LCD 细胞中。与顺铂联合使用时,D-allo 具有协同的生长抑制作用。D-allo 增加了硫氧还蛋白相互作用蛋白(TXNIP)的 mRNA 和蛋白表达。D-allo 降低了 G1 期细胞的比例,增加了 S 和 G2/M 期细胞的比例。在体内实验中,将 EBC1 细胞接种到 BALB/c-nu 小鼠中。肿瘤发生后,注射 D-allo 和顺铂。在这个小鼠异种移植模型中,与单独使用顺铂相比,联合使用 D-allo 显示出更大的肿瘤抑制作用,同时 Ki-67 降低,TXNIP 表达升高。总之,D-allo 抑制 NSCLC 细胞在体外增殖和体内肿瘤进展。与顺铂联合使用时,D-allo 具有额外的抗肿瘤作用。具体来说,TXNIP 表达增加和随后的 G2/M 期阻滞在 D-allo 介导的 NSCLC 抗肿瘤作用中起作用。

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