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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

Expression levels of GABA receptors in HCC. A: Expression levels of GABAA Rα3 (GABRA3) and GABAB R1 (GABBR1) protein in liver cancer cells. Cell lysates were examined by Western blot analysis using equal amounts of proteins. B, C, D: The relative mRNA expressions of GABAA receptor ε1 subunits, GABAB R1.2, and GABAB R1.4 in HCC and in adjacent non-tumorous liver tissue samples (NT) (n=50) were determined by quantitative real-time PCR.
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f1: Expression levels of GABA receptors in HCC. A: Expression levels of GABAA Rα3 (GABRA3) and GABAB R1 (GABBR1) protein in liver cancer cells. Cell lysates were examined by Western blot analysis using equal amounts of proteins. B, C, D: The relative mRNA expressions of GABAA receptor ε1 subunits, GABAB R1.2, and GABAB R1.4 in HCC and in adjacent non-tumorous liver tissue samples (NT) (n=50) were determined by quantitative real-time PCR.

Mentions: As of this writing, 16 human GABAA receptor subunits (α1-6, β1-3, γ1-3, δ, ε, π, and θ) and two human GABAB receptor subunits (R1 and R2) have been cloned [27, 28]. To identify the patterns of GABA receptor expression in HCC, the expression of GABA receptor subunits in various HCC cell lines was examined using real-time PCR and Western blot analysis. As shown in Figure 1A and Table 2, most cell lines express the GABAA receptor α3 and ε, and the GABAB R1 (BR1.2 and BR1.4) subunits. Therefore, the expression levels of the GABAA receptor α3 and ε, and the GABAB R1.2 and R1.4 subunits was determined in primary HCC tissues as well as adjacent NT liver tissues. The results revealed that the mRNA level of the GABAA receptor subunit ε1 was lower in HCC tissues than in NT liver tissues (Figure 1B, n=50), but no significant difference in the expression of the GABAA receptor α3 subunit was found between the two groups (data not shown). The mRNA levels of GABAB R1.2 and GABAB R1.4 were higher in HCC tissues than in NT liver tissues (Figure 1C). These data suggest the possible involvement of the GABAergic system in HCC.


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)

Expression levels of GABA receptors in HCC. A: Expression levels of GABAA Rα3 (GABRA3) and GABAB R1 (GABBR1) protein in liver cancer cells. Cell lysates were examined by Western blot analysis using equal amounts of proteins. B, C, D: The relative mRNA expressions of GABAA receptor ε1 subunits, GABAB R1.2, and GABAB R1.4 in HCC and in adjacent non-tumorous liver tissue samples (NT) (n=50) were determined by quantitative real-time PCR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC3643652&req=5

f1: Expression levels of GABA receptors in HCC. A: Expression levels of GABAA Rα3 (GABRA3) and GABAB R1 (GABBR1) protein in liver cancer cells. Cell lysates were examined by Western blot analysis using equal amounts of proteins. B, C, D: The relative mRNA expressions of GABAA receptor ε1 subunits, GABAB R1.2, and GABAB R1.4 in HCC and in adjacent non-tumorous liver tissue samples (NT) (n=50) were determined by quantitative real-time PCR.
Mentions: As of this writing, 16 human GABAA receptor subunits (α1-6, β1-3, γ1-3, δ, ε, π, and θ) and two human GABAB receptor subunits (R1 and R2) have been cloned [27, 28]. To identify the patterns of GABA receptor expression in HCC, the expression of GABA receptor subunits in various HCC cell lines was examined using real-time PCR and Western blot analysis. As shown in Figure 1A and Table 2, most cell lines express the GABAA receptor α3 and ε, and the GABAB R1 (BR1.2 and BR1.4) subunits. Therefore, the expression levels of the GABAA receptor α3 and ε, and the GABAB R1.2 and R1.4 subunits was determined in primary HCC tissues as well as adjacent NT liver tissues. The results revealed that the mRNA level of the GABAA receptor subunit ε1 was lower in HCC tissues than in NT liver tissues (Figure 1B, n=50), but no significant difference in the expression of the GABAA receptor α3 subunit was found between the two groups (data not shown). The mRNA levels of GABAB R1.2 and GABAB R1.4 were higher in HCC tissues than in NT liver tissues (Figure 1C). These data suggest the possible involvement of the GABAergic system in HCC.

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