Lunasin 增强奥沙利铂预防结肠癌转移生长的效果，与 α5β1 整合素结合并抑制 FAK/ERK/NF-κB 信号通路。

Lunasin potentiates the effect of oxaliplatin preventing outgrowth of colon cancer metastasis, binds to α5β1 integrin and suppresses FAK/ERK/NF-κB signaling.

机构信息

Department of Food Science and Human Nutrition, 228 ERML, MC-051, 1201 West Gregory Drive, Urbana, IL 61801, USA.

出版信息

Cancer Lett. 2011 Dec 27;313(2):167-80. doi: 10.1016/j.canlet.2011.09.002. Epub 2011 Sep 10.

DOI:10.1016/j.canlet.2011.09.002

PMID:21963225

Abstract

The effect of lunasin on colon cancer metastasis was studied using three human colon cancer cell lines in vitro and a liver metastasis model of colon cancer in vivo. Lunasin bound with α5β1 integrin and internalized into the nucleus of KM12L4 human colon cancer cells. Lunasin (10 μM) inhibited the activation of focal adhesion kinase (FAK) by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human colon cancer cells, respectively. Lunasin caused an increase in the expression of the inhibitor of kappa B alpha (IκB-α), a decrease in nuclear p50 NF-κB and a reduction in the migration of cancer cells. Lunasin (4 mg/kg bw) inhibited metastasis and potentiated the effect of oxaliplatin by reducing the expression of proliferating cell nuclear antigen. Liver metastatic nodules were reduced from 28 (PBS) to 14 (lunasin, P = 0.047) while combination of lunasin and oxaliplatin to 5 (P = 0.004). The tumor burden was reduced from 0.13 (PBS) to 0.10 (lunasin, P = 0.039) to 0.04 (lunasin + oxaliplatin, P < 0.0001). Moreover, lunasin potentiated the effect of oxaliplatin in modifying expression of proteins involved in apoptosis and metastasis including Bax, Bcl-2, IKK-α and p-p65. Lunasin inhibited metastasis of human colon cancer cells by direct binding with α5β1 integrin suppressing FAK/ERK/NF-κB signaling, and potentiated the effect of oxaliplatin in preventing the outgrowth of metastasis.

摘要

研究人员采用三种人结肠癌细胞系进行体外研究，并采用人结肠癌肝转移模型进行体内研究，探讨了亮抑酶肽对结肠癌转移的影响。亮抑酶肽与α5β1 整合素结合，并被内化到 KM12L4 人结肠癌细胞的细胞核中。亮抑酶肽（10 μM）分别抑制 RKO、HCT-116 和 KM12L4 人结肠癌细胞中粘着斑激酶（FAK）的激活 28%、39%和 60%。亮抑酶肽引起κB 抑制蛋白α（IκB-α）的表达增加，核 p50 NF-κB 减少，癌细胞迁移减少。亮抑酶肽（4mg/kg bw）通过降低增殖细胞核抗原的表达抑制转移，并增强奥沙利铂的作用。肝转移结节数从 28 个（PBS）减少到 14 个（亮抑酶肽，P=0.047），而亮抑酶肽与奥沙利铂联合治疗则减少到 5 个（P=0.004）。肿瘤负担从 0.13（PBS）减少到 0.10（亮抑酶肽，P=0.039）到 0.04（亮抑酶肽+奥沙利铂，P<0.0001）。此外，亮抑酶肽通过直接与α5β1 整合素结合抑制 FAK/ERK/NF-κB 信号通路，增强奥沙利铂对凋亡和转移相关蛋白表达的修饰作用，包括 Bax、Bcl-2、IKK-α 和 p-p65。亮抑酶肽通过直接与α5β1 整合素结合抑制 FAK/ERK/NF-κB 信号通路，抑制人结肠癌细胞的转移，并增强奥沙利铂抑制转移生长的作用。