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

D-阿洛糖与顺铂联合对非小细胞肺癌细胞的附加抗肿瘤作用

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作者:Nobuhiro Kanaji, Kazuyo Kamitori, Akram Hossain, Chisato Noguchi, Ayako Katagi, Norimitsu Kadowaki, Masaaki Tokuda

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.

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