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Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor.

Chen ZA, Bao MY, Xu YF, Zha RP, Shi HB, Chen TY, He XH - Cancer Biol Med (2012)

Bottom Line: The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

GABA-inhibited HCC migration and invasion. A, B: Migration and invasion assays were performed in SK-Hep1 cells stimulated with various concentrations of GABA (1 µM and 10 µM) for 24 h. Representative images are shown on the left, and the quantification of 5 randomly selected fields is shown on the right. C: Migration and invasion assays were performed in SMMC-7721 cells stimulated with GABA for 24 h. Data are representative of 3 independent experiments and are shown as means ± SEM. (*, P<0.05, **, P<0.01, by one-way ANOVA analysis).
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f2: GABA-inhibited HCC migration and invasion. A, B: Migration and invasion assays were performed in SK-Hep1 cells stimulated with various concentrations of GABA (1 µM and 10 µM) for 24 h. Representative images are shown on the left, and the quantification of 5 randomly selected fields is shown on the right. C: Migration and invasion assays were performed in SMMC-7721 cells stimulated with GABA for 24 h. Data are representative of 3 independent experiments and are shown as means ± SEM. (*, P<0.05, **, P<0.01, by one-way ANOVA analysis).

Mentions: To determine the effect of exogenous GABA on HCC cell metastasis, SK-Hep1 and SMMC-7721 cell lines with relatively high levels of GABAA and GABAB receptors (Figure 1A and Table 2) were treated with various concentrations of GABA without serum for 24 h. Cell proliferation and colony formation assays showed that GABA has no impact on liver cancer cell growth (data not shown). A filter with or without matrigel coating was used as a model for the basement membrane. The number of cells that invaded the lower compartment of the chamber through the filter with GABA stimulation was significantly lower than that in the cells without GABA (Figure 2), indicating that GABA decreases cell migration and invasion.


Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor.

Chen ZA, Bao MY, Xu YF, Zha RP, Shi HB, Chen TY, He XH - Cancer Biol Med (2012)

GABA-inhibited HCC migration and invasion. A, B: Migration and invasion assays were performed in SK-Hep1 cells stimulated with various concentrations of GABA (1 µM and 10 µM) for 24 h. Representative images are shown on the left, and the quantification of 5 randomly selected fields is shown on the right. C: Migration and invasion assays were performed in SMMC-7721 cells stimulated with GABA for 24 h. Data are representative of 3 independent experiments and are shown as means ± SEM. (*, P<0.05, **, P<0.01, by one-way ANOVA analysis).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643652&req=5

f2: GABA-inhibited HCC migration and invasion. A, B: Migration and invasion assays were performed in SK-Hep1 cells stimulated with various concentrations of GABA (1 µM and 10 µM) for 24 h. Representative images are shown on the left, and the quantification of 5 randomly selected fields is shown on the right. C: Migration and invasion assays were performed in SMMC-7721 cells stimulated with GABA for 24 h. Data are representative of 3 independent experiments and are shown as means ± SEM. (*, P<0.05, **, P<0.01, by one-way ANOVA analysis).
Mentions: To determine the effect of exogenous GABA on HCC cell metastasis, SK-Hep1 and SMMC-7721 cell lines with relatively high levels of GABAA and GABAB receptors (Figure 1A and Table 2) were treated with various concentrations of GABA without serum for 24 h. Cell proliferation and colony formation assays showed that GABA has no impact on liver cancer cell growth (data not shown). A filter with or without matrigel coating was used as a model for the basement membrane. The number of cells that invaded the lower compartment of the chamber through the filter with GABA stimulation was significantly lower than that in the cells without GABA (Figure 2), indicating that GABA decreases cell migration and invasion.

Bottom Line: The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus