Inhibition of PARP1 activity enhances chemotherapeutic efficiency in cisplatin-resistant gastric cancer cells
| Autor: | Danping Qiu, Sapna Panday, Qiang Wang, Wenxia Xu, Jianwei Zhou, Qi Chen, Aiping Li, Donglin Yan, Shouyu Wang, Jianping Xiong, Zhangding Wang, Xue Zhao |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
DNA End-Joining Repair DNA damage Poly (ADP-Ribose) Polymerase-1 Drug resistance Biology Pharmacology Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine PARP1 Stomach Neoplasms Cell Line Tumor medicine Humans Enzyme Inhibitors Protein Kinase C Cisplatin Cancer Cell Biology medicine.disease 030104 developmental biology chemistry Apoptosis Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell DNA medicine.drug DNA Damage |
| Zdroj: | The international journal of biochemistrycell biology. 92 |
| ISSN: | 1878-5875 |
| Popis: | Cisplatin (DDP) is the first line chemotherapeutic drug for several cancers, including gastric cancer (GC). Unfortunately, the rapid development of drug resistance remains a significant challenge for the clinical application of cisplatin. There is an urgent need to develop new strategies to overcome DDP resistance for cancer treatment. In this study, four types of human GC cells have been divided into naturally sensitive or naturally resistant categories according to their responses to cisplatin. PARP1 activity (poly (ADP-ribose), PAR) was found to be greatly increased in cisplatin-resistant GC cells. PARP1 inhibitors significantly enhanced cisplatin-induced DNA damage and apoptosis in the resistant GC cells via the inhibition of PAR. Mechanistically, PARP1 inhibitors suppress DNA-PKcs stability and reduce the capability of DNA double-strand break (DSB) repair via the NHEJ pathway. This was also verified in BGC823/DDP GC cells with acquired cisplatin resistance. In conclusion, we identified that PARP1 is a useful interceptive target in cisplatin-resistant GC cells. Our data provide a promising therapeutic strategy against cisplatin resistance in GC cells that has potential translational significance. |
| Databáze: | OpenAIRE |
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