Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels
| Autor: | Feng He, Fang Wei, Shanqi Zeng, Ping Yang, Jianchang Wei, Jie Cao, Chengxing Wang, Wanglin Li, Wensong Cai, Di Huang, Tong Zhang, Qiang Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Cell colorectal cancer Flow cytometry resistance 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Oncogene medicine.diagnostic_test gambogic acid oxaliplatin Articles Cell cycle Molecular biology 030104 developmental biology medicine.anatomical_structure Oncology chemistry Cell culture Apoptosis 030220 oncology & carcinogenesis Gambogic acid Intracellular |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| Popis: | Resistance to oxaliplatin (L-OHP) is a major obstacle to successful chemotherapy in colorectal cancer (CRC). In the present study, the ability of gambogic acid (GA) to reverse L-OHP resistance in CRC LoVo cells was investigated. L-OHP-resistant LoVo/L-OHP cells were established by exposing them to increasing concentrations of L-OHP. GA-reversed L-OHP-sensitive LoVo/L-OHP/GA cells were established by exposure to 0.5 µmol/l GA for 2 weeks. A Cell Counting Kit-8 assay was used to assess levels of proliferation. Flow cytometry was applied to detect apoptosis rates. Transwell assays were used to analyse invasion. Inductively coupled plasma mass spectrometry was used to determine intracellular platinum (Pt) content. Western blot analysis was used to reveal the protein levels of Human copper transporter 1 (hCTR1), Copper-transporting p-type adenosine triphosphatases 1 (ATP7A) and Copper-transporting p-type adenosine triphosphatases 2 (ATP7B). LoVo/L-OHP and LoVo/L-OHP/GA cell lines were successfully established, and it was identified that L-OHP inhibited the proliferation of LoVo, LoVo/L-OHP and LoVo/L-OHP/GA cells in a dose-dependent manner. Compared with the parent LoVo cells, the anti-apoptosis and invasion properties of LoVo/L-OHP cells were enhanced, and were reversed by GA treatment. Intracellular Pt content was highest in the LoVo cells, followed by LoVo/L-OHP/GA cells, and then lowest in the LoVo/L-OHP cells. Downregulated hCTP1 and upregulated ATP7A and ATP7B were associated with L-OHP resistance, and GA reversed the resistance by increasing levels of hCTR1 and decreasing levels of ATP7A and ATP7B. In conclusion, GA has the potential ability to reverse L-OHP resistance in CRC cells by increasing intracellular Pt content, which it achieves by increasing hCTR1 levels and decreasing ATP7A and ATP7B levels. GA may represent a promising treatment agent for L-OHP resistance. |
| Databáze: | OpenAIRE |
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