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外源性胰岛素样生长因子结合蛋白7抑制人乳腺癌MDA-MB-453细胞的增殖

袁磊, 范文娟, 杨旭光, 饶淑梅, 宋金玲, 宋国华^*

漯河医学高等专科学校分子生物学实验室，漯河 462002

摘要

为了探究外源性胰岛素样生长因子结合蛋白7 (insulin-like growth factor binding protein 7, IGFBP7)对人乳腺癌MDA-MB-453细胞增殖的影响及其分子生物学机制，本研究通过四甲基偶氮唑蓝(MTT)实验揭示外源性IGFBP7对人乳腺癌MDA-MB-453细胞增殖有显著的抑制作用(IGFBP7的IC50 = 8.49 μg/mL)，并呈剂量和时间的双重依赖性，该作用可被p38MAPK阻断剂SB203580抑制。流式细胞术检测结果表明，外源性IGFBP7可有效阻止MDA-MB-453细胞从G1期进入S期。Western blot进一步检测了外源性IGFBP7对p38MAPK、p-p38MAPK、p21CIP1/WAF1、Rb和p-Rb蛋白水平的影响。外源性IGFBP7可促进p38MAPK磷酸化和p21CIP1/WAF1蛋白的表达，抑制Rb磷酸化，而SB203580能够抑制外源性IGFBP7对人乳腺癌MDA-MB-453 细胞p21CIP1/WAF1蛋白表达和Rb磷酸化的影响。以上结果表明，外源性IGFBP7可通过激活p38MAPK信号通路，上调p21CIP1/WAF1蛋白表达和抑制Rb磷酸化，以阻滞人乳腺癌MDA-MB-453细胞于G1期。

关键词： 胰岛素样生长因子结合蛋白7; MDA-MB-453; 细胞增殖; p38MAPK; p21CIP1/WAF1

分类号：R737.9

[Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism ] [Article in Chinese]

YUAN Lei, FAN Wen-Juan, YANG Xu-Guang, RAO Shu-Mei, SONG Jin-ling, SONG Guo-Hua ^*

Laboratory of Molecular Biology, Luohe Medical College, Luohe 462002, China

Abstract

The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 μg/mL) in time- and concentration-dependent manner. SB203580, p38^MAPK inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38^MAPK, up-regulated expression of p21^CIP1/WAF1, and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21^CIP1/WAF1 and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38^MAPK signaling pathway, upregulate p21^CIP1/WAF1 expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.

Key words: insulin-like growth factor binding protein 7; MDA-MB-453; proliferation; p38MAPK; p21CIP1/WAF1

收稿日期：2013-03-30　　录用日期：2013-06-19

通讯作者：宋国华　　E-mail: lhyzsgh@163.com

引用本文：

袁磊, 范文娟, 杨旭光, 饶淑梅, 宋金玲, 宋国华. 外源性胰岛素样生长因子结合蛋白7抑制人乳腺癌MDA-MB-453细胞的增殖[J]. 生理学报 2013; 65 (5): 519-524.

YUAN Lei, FAN Wen-Juan, YANG Xu-Guang, RAO Shu-Mei, SONG Jin-ling, SONG Guo-Hua . [Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism ] [Article in Chinese]. Acta Physiol Sin 2013; 65 (5): 519-524 (in Chinese with English abstract).