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Increase in CIP2A expression is associated with cisplatin chemoresistance in gastric cancer
Juanli Ji1,2,1, Weiguo Zhen1,1, Yuan Si1
1Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
Background:
The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which involves in the progression of several human malignancies. Development of cisplatin (DDP) resistance is the obstacle to an effective control of gastric cancer (GC) clinically.
Objective:
We thus assessed whether CIP2A expression is associated with sensitivity of GC to DDP.
Methods:
Real-time quantitative PCR, immunohistochemical analysis, or western blotting was performed to detect CIP2A expression in GC patients' tissues. SGC7901/DDP cells were transfected with CIP2A siRNA. MTT assay was used to determine the DDP-sensitivity of cells. Flow cytometry was used to measure cell apoptosis.
Results:
CIP2A has higher expression in DDP-resistant GC patients. DDP-resistant GC patients with high CIP2A expression presented with poorer overall survival rates than those with low CIP2A expression. CIP2A knockdown in DDP-resistant GC cells resulted in attenuated proliferative abilities and increased apoptosis level. CIP2A depletion sensitizes DDP-resistant cells to DDP and CIP2A overexpression antagonizes DDP-sensitive cells to DDP. CIP2A influences the expression of multidrug resistance-related proteins in GC cells.
Conclusions:
Our results suggested that CIP2A oncoprotein plays an important role in DDP resistance of GC and could serve as a novel therapeutic target for the treatment of GC patients with DDP resistance.
Insights
Cancerous inhibitor of protein phosphatase 2A (CIP2A) drives cisplatin resistance in gastric cancer (GC). Reducing CIP2A in resistant GC cells enhances cisplatin sensitivity and apoptosis, identifying CIP2A as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein implicated in various human cancers.
- Cisplatin (DDP) resistance poses a significant challenge in the clinical management of gastric cancer (GC).
Purpose of the Study:
- To investigate the association between CIP2A expression and sensitivity to DDP in gastric cancer.
- To evaluate CIP2A as a potential therapeutic target for overcoming DDP resistance in GC.
Main Methods:
- CIP2A expression was analyzed in GC tissues using real-time quantitative PCR, immunohistochemistry, and western blotting.
- Gastric cancer cells (SGC7901/DDP) were transfected with CIP2A siRNA to assess the impact of knockdown on DDP sensitivity, proliferation, and apoptosis.
- MTT assays and flow cytometry were employed to quantify DDP sensitivity and apoptosis levels, respectively.
Main Results:
- Higher CIP2A expression was observed in DDP-resistant GC patients, correlating with poorer survival rates.
- Knockdown of CIP2A in DDP-resistant GC cells reduced proliferation and increased apoptosis.
- CIP2A depletion sensitized DDP-resistant cells to DDP, while its overexpression antagonized DDP sensitivity in sensitive cells, influencing multidrug resistance-related proteins.
Conclusions:
- CIP2A plays a critical role in mediating DDP resistance in gastric cancer.
- CIP2A represents a promising therapeutic target for enhancing the efficacy of DDP treatment in resistant GC patients.
