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支链氨基酸通过诱导自噬抑制人癌细胞中胰岛素引发的增殖。

Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.

机构信息

Department of Surgery, The University of Tokushima, Tokushima, Japan.

Department of Immunology and Parasitology, The University of Tokushima, Tokushima, Japan.

出版信息

Anticancer Res. 2014 Sep;34(9):4789-96.

Abstract

BACKGROUND

Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear.

MATERIALS AND METHODS

Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively.

RESULTS

BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1).

CONCLUSION

BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions.

摘要

背景

支链氨基酸(BCAA)饮食补充剂可抑制糖尿病动物模型中胰岛素样生长因子(IGF)/IGF-I 受体(IGF-IR)轴的激活。然而,在高胰岛素血症条件下,BCAA 对人癌细胞系的体外影响尚不清楚。

材料与方法

用不同浓度的 BCAA 处理结肠(HCT-116)和肝(HepG2)肿瘤细胞,有或没有氟尿嘧啶(5-FU)。测定 BCAA 对胰岛素起始增殖的影响。通过定量实时聚合酶链反应(qRT-PCR)和 Western blot 分别分析基因和蛋白表达。

结果

BCAA 补充对细胞增殖没有显著影响,与 5-FU 也没有明显的协同或拮抗作用。然而,BCAA 显著降低了体外人结肠和肝癌细胞系中胰岛素起始的增殖。BCAA 补充导致激活的 IGF-IR 表达明显下降,并显著增强了 LC3-II 和 BECN1(BECLIN-1)的 mRNA 和蛋白表达。

结论

BCAA 可能是高胰岛素血症条件下癌症的一种有用的化学预防方式。

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