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Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels

  • Authors:
    • Qiang Wang
    • Jianchang Wei
    • Chengxing Wang
    • Tong Zhang
    • Di Huang
    • Fang Wei
    • Feng He
    • Wensong Cai
    • Ping Yang
    • Shanqi Zeng
    • Wanglin Li
    • Jie Cao
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2366-2372
    |
    Published online on: June 6, 2018
       https://doi.org/10.3892/ol.2018.8916
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Wang Q, Wei J, Wang C, Zhang T, Huang D, Wei F, He F, Cai W, Yang P, Zeng S, Zeng S, et al: Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels. Oncol Lett 16: 2366-2372, 2018.
APA
Wang, Q., Wei, J., Wang, C., Zhang, T., Huang, D., Wei, F. ... Cao, J. (2018). Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels. Oncology Letters, 16, 2366-2372. https://doi.org/10.3892/ol.2018.8916
MLA
Wang, Q., Wei, J., Wang, C., Zhang, T., Huang, D., Wei, F., He, F., Cai, W., Yang, P., Zeng, S., Li, W., Cao, J."Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels". Oncology Letters 16.2 (2018): 2366-2372.
Chicago
Wang, Q., Wei, J., Wang, C., Zhang, T., Huang, D., Wei, F., He, F., Cai, W., Yang, P., Zeng, S., Li, W., Cao, J."Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels". Oncology Letters 16, no. 2 (2018): 2366-2372. https://doi.org/10.3892/ol.2018.8916
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Q, Wei J, Wang C, Zhang T, Huang D, Wei F, He F, Cai W, Yang P, Zeng S, Zeng S, et al: Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels. Oncol Lett 16: 2366-2372, 2018.
APA
Wang, Q., Wei, J., Wang, C., Zhang, T., Huang, D., Wei, F. ... Cao, J. (2018). Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels. Oncology Letters, 16, 2366-2372. https://doi.org/10.3892/ol.2018.8916
MLA
Wang, Q., Wei, J., Wang, C., Zhang, T., Huang, D., Wei, F., He, F., Cai, W., Yang, P., Zeng, S., Li, W., Cao, J."Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels". Oncology Letters 16.2 (2018): 2366-2372.
Chicago
Wang, Q., Wei, J., Wang, C., Zhang, T., Huang, D., Wei, F., He, F., Cai, W., Yang, P., Zeng, S., Li, W., Cao, J."Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels". Oncology Letters 16, no. 2 (2018): 2366-2372. https://doi.org/10.3892/ol.2018.8916
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