通过 GABA A 受体抑制人肝癌细胞迁移和侵袭。
Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor.
机构信息
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
出版信息
Cancer Biol Med. 2012 Jun;9(2):90-8. doi: 10.3969/j.issn.2095-3941.2012.02.002.
OBJECTIVE
To investigate the roles of the γ-aminobutyric acid (GABA) in the metastasis of hepatocellular carcinoma (HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC.
METHODS
The expression levels of GABA receptor subunit genes in various HCC cell lines and patients' tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer.
RESULTS
The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABAA receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo.
CONCLUSIONS
These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system.
目的
探讨γ-氨基丁酸（GABA）在肝细胞癌（HCC）转移中的作用，并探索一种治疗 HCC 的新的潜在治疗方法。
方法
通过实时定量聚合酶链反应和 Western blot 分析检测不同 HCC 细胞系和患者组织中 GABA 受体亚基基因的表达水平。通过 Transwell 细胞迁移和侵袭实验进行功能分析。通过免疫荧光染色确定 GABA 对肝癌细胞细胞骨架的影响。并通过体内肝癌原位模型评估 GABA 对 HCC 转移的影响。
结果
GABA 受体亚基的 mRNA 水平在原发性肝癌组织和相邻非肿瘤肝组织之间存在差异。GABA 通过诱导肝癌细胞细胞骨架重排，通过离子型 GABAA 受体抑制人肝癌细胞的迁移和侵袭。GABA 的预处理还显著减少了体内肝内肝转移和原发性肿瘤的形成。
结论
这些发现为基于 GABA 能系统调节的癌症患者治疗提供了一种潜在的新的治疗方法。
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