Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting proliferation and inducing apoptosis

  • Authors:
    • Jianchang Wei
    • Ping Yang
    • Wanglin Li
    • Feng He
    • Shanqi Zeng
    • Tong Zhang
    • Junbin Zhong
    • Di Huang
    • Zhuanpeng Chen
    • Chengxing Wang
    • Huacui Chen
    • He Hu
    • Jie Cao
  • View Affiliations

  • Published online on: January 2, 2017     https://doi.org/10.3892/etm.2017.4021
  • Pages: 662-668
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Abstract

Chemotherapy using 5-fluorouracil (5-FU) for colorectal cancer (CRC) has low specificity and response rates, leading to severe side effects. Gambogic acid (GA), a traditional Chinese medicine, has multi‑targeted anticancer effects, including growth inhibition and apoptosis induction. However, it is unclear whether a combination of 5‑FU and GA has synergistic anticancer effects in CRC cells. In this study, SW480 and HCT116 human CRC cells and human intestinal epithelial cells (IECs) were treated with different concentrations of 5‑FU, GA or 5‑FU+GA. A Cell Counting kit‑8 assay was conducted to quantify cell proliferation. The combination index (CI) was calculated and the median‑effect principle was applied to analyze the interaction between 5‑FU and GA. Flow cytometry was used to determine the percentage of cells undergoing apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blotting were applied to measure P53, survivin and thymidylate synthase (TS) mRNA and protein levels. It was found that 5‑FU+GA more pronouncedly inhibited cell growth and induced apoptosis, compared with either monotherapy. CI values <1 indicated the synergistic effects of the drugs. 5‑FU+GA further decreased P53, survivin and TS mRNA and protein levels in the two CRC cell lines compared with single drugs, whereas increased P53 protein levels were observed in HCT116 cells. Moreover, 5‑FU+GA did not increase cytotoxicity to IECs. These results demonstrate that GA enhances the anticancer effects of 5‑FU on CRC cells. Combined treatment with 5‑FU and GA is effective and safe for CRC cells, and may become a promising chemotherapy treatment.

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February-2017
Volume 13 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wei J, Yang P, Li W, He F, Zeng S, Zhang T, Zhong J, Huang D, Chen Z, Wang C, Wang C, et al: Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting proliferation and inducing apoptosis. Exp Ther Med 13: 662-668, 2017.
APA
Wei, J., Yang, P., Li, W., He, F., Zeng, S., Zhang, T. ... Cao, J. (2017). Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting proliferation and inducing apoptosis. Experimental and Therapeutic Medicine, 13, 662-668. https://doi.org/10.3892/etm.2017.4021
MLA
Wei, J., Yang, P., Li, W., He, F., Zeng, S., Zhang, T., Zhong, J., Huang, D., Chen, Z., Wang, C., Chen, H., Hu, H., Cao, J."Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting proliferation and inducing apoptosis". Experimental and Therapeutic Medicine 13.2 (2017): 662-668.
Chicago
Wei, J., Yang, P., Li, W., He, F., Zeng, S., Zhang, T., Zhong, J., Huang, D., Chen, Z., Wang, C., Chen, H., Hu, H., Cao, J."Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting proliferation and inducing apoptosis". Experimental and Therapeutic Medicine 13, no. 2 (2017): 662-668. https://doi.org/10.3892/etm.2017.4021