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Updated: May 12, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
GABAA receptor-binding protein promotes sensitivity to apoptosis induced by chemotherapeutic agents
Seung Bae Rho1, Hyun-Jung Byun, Boh-Ram Kim
1Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea. sbrho@ncc.re.kr
Abstract:
In the present study, the expression of human γ-aminobutyrate type A (GABAA) receptor-binding protein (GABARBP) is downregulated in ovarian cancer cell lines and tissues. We also found that the specific function of GABAPBP was that of a novel pro-apoptotic protein. Both GABARBP and cisplatin suppressed cancer cell proliferation in a concentration-dependent manner. The combined treatment of GABARBP and cisplatin was more effective in inhibiting cell growth, as well as cell migration, than with either drug treatment alone. At the same time, the treatment combination is correlated with the downregulation of cyclin D1 and CDK4, arrested cell cycle progression in the G₀-G₁ phase and enhancing p53 expression, while also reducing Bcl-2 and Bcl-xL expression. The p53 and p21 promoter luciferase activities were induced by GABARBP, whereas there was no effect on the p53-/- and p21-/- system. In addition, p53 activity was validated with UV irradiation and siGABARBP. Taken together, our results indicate that GABARBP can regulate the pro-apoptotic activity of cisplatin via the upregulation of p53 expression.
Insights
Human gamma-aminobutyrate type A receptor-binding protein (GABARBP) acts as a pro-apoptotic protein in ovarian cancer. Combined with cisplatin, GABARBP enhances apoptosis and inhibits cancer cell proliferation and migration.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ovarian cancer remains a significant health challenge with limited treatment options.
- Understanding novel therapeutic targets and mechanisms is crucial for improving patient outcomes.
- The role of gamma-aminobutyrate type A receptor-binding protein (GABARBP) in cancer is not fully elucidated.
Purpose of the Study:
- To investigate the expression and function of GABARBP in ovarian cancer.
- To evaluate the potential of GABARBP as a therapeutic agent, alone and in combination with cisplatin.
- To elucidate the molecular mechanisms underlying GABARBP's effects on ovarian cancer cells.
Main Methods:
- Analysis of GABARBP expression in ovarian cancer cell lines and tissues.
- Cell proliferation, migration, and apoptosis assays.
- Western blotting to assess protein expression levels (cyclin D1, CDK4, p53, p21, Bcl-2, Bcl-xL).
- Luciferase reporter assays to evaluate promoter activity (p53, p21).
- Validation of p53 activity using UV irradiation and small interfering RNA (siGABARBP).
Main Results:
- GABARBP expression is downregulated in ovarian cancer.
- GABARBP exhibits pro-apoptotic properties and suppresses cancer cell proliferation and migration.
- Combined treatment with GABARBP and cisplatin demonstrates synergistic effects on inhibiting cell growth and migration.
- The combination therapy downregulates cyclin D1 and CDK4, arrests the cell cycle in G₀-G₁, and modulates apoptosis-related proteins (p53, p21, Bcl-2, Bcl-xL).
- GABARBP induces p53 and p21 promoter activity, indicating a role in p53-mediated apoptosis.
Conclusions:
- GABARBP is a novel pro-apoptotic protein with potential in ovarian cancer therapy.
- GABARBP enhances the anti-cancer effects of cisplatin through p53-dependent pathways.
- Targeting GABARBP may represent a promising strategy for ovarian cancer treatment.
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