Abstract
Objective
Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This study aimed to clarify the role and mechanism of runt-related transcription factor 2 (RUNX2) in platinum-based chemotherapy resistance.
Methods
First, a drug-resistant model of gastric cancer cells was established to evaluate the relative expression level of the RUNX2 as a potential biomarker of chemotherapy resistance. Next, exogenous silencing was conducted to study whether RUNX2 could reverse drug resistance and understand the underlying mechanisms. Simultaneously, the correlation between the clinical outcomes of 40 patients after chemotherapy and the RUNX2 expression levels in tumor samples was analyzed.
Results
We discovered that RUNX2 was significantly expressed in drug-resistant gastric cancer cells and tissues; it was also reversibly resistant to transformation treatment by exogenous RUNX2 silencing. It is confirmed that RUNX2 negatively regulates the apoptosis pathway of the p53 to reduce the chemotherapeutic effects of gastric cancer.
Conclusion
RUNX2 is a possible target for platinum-based chemotherapy resistance.
Abbreviations
RUNX2, Runt-related transcription factor 2; CCK-8, Cell Counting Kit-8; qRT-PCR, quantitative real-time polymerase chain reaction; WB, Western blot; DDP, Cisplatin; RIPA, Radio Immunoprecipitation Assay; ADR, Adriamycin; V–fluorescein isothiocyanate, (V-FITC); propidium iodide, PI; PMAIP1, phorbol-12-myristate-13-acetate-induced protein 1; IHC, immunohistochemistry.
Acknowledgments
We appreciate all the laboratory members for their valuable suggestions and kind help.
Ethics Approval
This study was approved by the Ethics Committee of Baotou Central Hospital (Date18-Sep-2021/No KYLL2021 005). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants signed written informed consent.
Disclosure
The authors declare that they have no competing interests in this work.