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AT-rich interactive domain1A determines sensitivity to oxaliplatin in gastric cancer cells
Qing Liu1, Qing-Qing Weng2, Song-Fei Shen1
1Department of Oncology, Union Medical College Hospital, Fujian Medical University, Fuzhou, China.
Background:
Gastric cancer is a highly heterogeneous disease and its traditional histopathological classification is difficult to meet clinical needs. Oxaliplatin is an antitumor drug with high efficiency and low toxicity. Therefore, the insensitivity or secondary drug resistance of oxaliplatin to gastric cancer is vital for tumor progression. The aim of this study was to investigate the sensitivity of gastric cancer cells to oxaliplatin after ARID1A (AT-rich interactive domain1A gene) gene silencing.
Methods:
MGC-803 and AGS cells were selected as gastric cancer cells for study. ARID1A protein and mRNA expression was detected by Western blot and quantitative reverse-transcription PCR (qRT-PCR). The short hairpin RNA (shRNA) fragment of ARID1A gene silencing was constructed and introduced into gastric cancer cells. The cell proliferation activity was calculated using CCK8 and the IC50 was calculated. The flow cytometry was used to detect the cell cycle and apoptosis rate. The ability of cell invasion was detected by transwell method. Cells were treated with different concentrations of oxaliplatin.
Results:
The proliferation of gastric cancer cells was promoted by ARID1A gene silencing (P<0.01), the quantity of cells in S phase increased (P<0.05), and the invasive ability increased (P<0.05). After treatment with oxaliplatin at different concentrations, ARID1A gene silencing reduced the inhibition rate of oxaliplatin on gastric cancer cells and apoptosis rate (P<0.05), and increased IC 50 (P<0.01).
Conclusions:
ARID1A gene silencing, a factor promoting proliferation of gastric cancer cells, would reduce the sensitivity of gastric cancer cells to oxaliplatin, which can provide a basis for the exploration of targeted drugs for individualized treatment of gastric cancer.
Insights
Gastric cancer cell proliferation and invasion increase with ARID1A gene silencing. This silencing reduces gastric cancer cell sensitivity to oxaliplatin, impacting treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer is a complex disease with limitations in traditional classification.
- Oxaliplatin is an effective chemotherapy drug, but resistance is a clinical challenge.
- Understanding factors influencing oxaliplatin resistance is crucial for improving gastric cancer treatment.
Purpose of the Study:
- To investigate the effect of AT-rich interactive domain 1A (ARID1A) gene silencing on gastric cancer cell sensitivity to oxaliplatin.
- To determine how ARID1A gene silencing influences gastric cancer cell proliferation, cell cycle, apoptosis, and invasion.
Main Methods:
- Gastric cancer cell lines (MGC-803 and AGS) were used.
- ARID1A gene silencing was achieved using short hairpin RNA (shRNA).
- Cell proliferation (CCK8), IC50, cell cycle, apoptosis (flow cytometry), and invasion (Transwell assay) were assessed after oxaliplatin treatment.
Main Results:
- ARID1A gene silencing significantly increased gastric cancer cell proliferation and invasion.
- Silencing ARID1A led to an increased proportion of cells in the S phase.
- Oxaliplatin treatment showed reduced efficacy in ARID1A-silenced cells, indicated by lower inhibition rates, reduced apoptosis, and increased IC50 values.
Conclusions:
- ARID1A gene silencing promotes gastric cancer cell proliferation and invasion.
- Reduced ARID1A expression diminishes gastric cancer cell sensitivity to oxaliplatin.
- Targeting ARID1A may offer a strategy for overcoming oxaliplatin resistance in personalized gastric cancer therapy.
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