Upregulation of GRIM-19 augments the sensitivity of prostate cancer cells to docetaxel by targeting Rad23b
| Autor: | Linyong Liu, Zaixiong Shen, Hai-li Lin, Hong Chen, Liutao Luo, Jiangui Lin, Hongjie Liu, Minggen Yang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male animal structures DNA Repair Physiology DNA damage medicine.medical_treatment Down-Regulation Apoptosis Docetaxel 03 medical and health sciences Prostate cancer 0302 clinical medicine Downregulation and upregulation Western blot Physiology (medical) Cell Line Tumor medicine Humans NADH NADPH Oxidoreductases Aged Pharmacology Chemotherapy medicine.diagnostic_test Chemistry fungi Prostatic Neoplasms Middle Aged medicine.disease Up-Regulation body regions DNA-Binding Proteins Gene Expression Regulation Neoplastic 030104 developmental biology DNA Repair Enzymes Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis PC-3 Cells Cancer research Apoptosis Regulatory Proteins medicine.drug DNA Damage |
| Zdroj: | Clinical and experimental pharmacologyphysiologyREFERENCES. 47(1) |
| ISSN: | 1440-1681 |
| Popis: | The gene associated with retinoid-interferon mortality (GRIM-19) has been reported to be correlated with drug resistance, whereas its functional role in prostate cancer (PC) is not fully understood. This study aims to clarify the potential role and molecular mechanisms of GRIM-19 on the response of PC cells to chemical drug docetaxel. mRNA and protein level of GRIM-19 expression in cells and tissues of PC were measured by quantitative real-time PCR and western blot, respectively. Knock-down of GRIM-19 in PC cells was performed using siRNA. Cell apoptosis was determined by flow cytometric analysis. DNA damage in PC cells was detected by γ-H2AX staining. GRIM-19 was downregulated in PC tissues and cell lines. Knock-down of GRIM-19 increased the resistance of PC cells to docetaxel, and overexpression of GRIM-19 promoted docetaxel-induced apoptotic death in PC cells. Mechanistically, GRIM-19 downregulated the expression of the survival gene Rad23b, which promoted DNA damage repair. Overexpression of Rad23b reversed GRIM-19-mediated response to docetaxel in PC cells. GRIM-19 promoted the sensitivity of PC cells to docetaxel by downregulating Rad23b, which may serve as a promising target to develop a better strategy of chemotherapy for PC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text