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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-induced actin cytoskeleton reorganization. SMMC-7721 cells grown on an eight-well CultureSlide were fixed with 3.4% paraformaldehyde in PBS and then immunostained with Alexa Fluor® 594 phalloidin (red), α-tubulin mouse monoclonal antibody (green), and DAPI (blue). Cytoskeletal changes occurred when the cells were stimulated with GABA. Scale bar=10 µm.
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f4: GABA-induced actin cytoskeleton reorganization. SMMC-7721 cells grown on an eight-well CultureSlide were fixed with 3.4% paraformaldehyde in PBS and then immunostained with Alexa Fluor® 594 phalloidin (red), α-tubulin mouse monoclonal antibody (green), and DAPI (blue). Cytoskeletal changes occurred when the cells were stimulated with GABA. Scale bar=10 µm.

Mentions: The actin cytoskeleton reportedly plays an important role in coordinating cell migration. Thus, the cytoskeletal changes were examined after the SMMC-7721 cells were stimulated with GABA. Figure 4 shows that cytoskeletal changes occurred when the cells were stimulated with GABA. A comparison of the pretreated and control groups clearly demonstrated a decrease in the number of actin fibers in the cells stimulated with GABA. In addition, actin filaments were well organized only in GABA-treated cells. A type of F-actin stress fiber was observed in the control cells. Thus, these data verify that GABA regulates the formation of actin fibers.


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-induced actin cytoskeleton reorganization. SMMC-7721 cells grown on an eight-well CultureSlide were fixed with 3.4% paraformaldehyde in PBS and then immunostained with Alexa Fluor® 594 phalloidin (red), α-tubulin mouse monoclonal antibody (green), and DAPI (blue). Cytoskeletal changes occurred when the cells were stimulated with GABA. Scale bar=10 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: GABA-induced actin cytoskeleton reorganization. SMMC-7721 cells grown on an eight-well CultureSlide were fixed with 3.4% paraformaldehyde in PBS and then immunostained with Alexa Fluor® 594 phalloidin (red), α-tubulin mouse monoclonal antibody (green), and DAPI (blue). Cytoskeletal changes occurred when the cells were stimulated with GABA. Scale bar=10 µm.
Mentions: The actin cytoskeleton reportedly plays an important role in coordinating cell migration. Thus, the cytoskeletal changes were examined after the SMMC-7721 cells were stimulated with GABA. Figure 4 shows that cytoskeletal changes occurred when the cells were stimulated with GABA. A comparison of the pretreated and control groups clearly demonstrated a decrease in the number of actin fibers in the cells stimulated with GABA. In addition, actin filaments were well organized only in GABA-treated cells. A type of F-actin stress fiber was observed in the control cells. Thus, these data verify that GABA regulates the formation of actin fibers.

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