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Synergistic effect of kaempferol and 5‑fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway

  • Authors:
    • Qiongyu Li
    • Lihui Wei
    • Shan Lin
    • Youqin Chen
    • Jiumao Lin
    • Jun Peng

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  • Published online on: May 27, 2019     https://doi.org/10.3892/mmr.2019.10296
  • Pages: 728-734
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Combination chemotherapy with chemosensitizers can exert synergistic therapeutic effects, reduce toxicity, and delay the induction of drug resistance. In the present study, the antitumor effects were investigated, and the possible underlying mechanisms of kaempferol combined with 5‑fluorouracil (5‑FU) in colorectal cancer cells were explored. HCT‑8 or HCT‑116 cells were treated with various concentrations of kaempferol and/or 5‑FU for the indicated time‑points. An MTT assay was used to determine cell viability, whereas the synergistic effects were assessed by calculating the combination indices of kaempferol and 5‑FU. Annexin V analysis and Hoechst staining were used to determine cell apoptosis. q‑PCR and western blotting were performed to determine the expression levels of Bax, Bcl‑2, thymidylate synthase (TS), PTEN, PI3K, AKT, and p‑AKT. The combination of kaempferol and 5‑FU was determined to be more effective in inhibiting cell viability than either of the agents alone. The inhibition of tumors in response to kaempferol and 5‑FU was associated with the reduction in proliferation ability and stimulation of apoptosis. The protein results indicated that kaempferol and 5‑FU could significantly upregulate the expression levels of Bax and downregulate the expression levels of Bcl‑2 and TS. Furthermore, the combination treatment greatly inhibited the activation of the PI3K/Akt pathway, suggesting the involvement of this pathway in the synergistic effects. The present study demonstrated that kaempferol has a synergistic effect with 5‑FU by inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells via suppression of TS or attenuation of p‑Akt activation. The combination of kaempferol and 5‑FU may be used as an effective therapeutic strategy for colorectal cancer.
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July-2019
Volume 20 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • Journal Metrics
  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 7.6
  • CiteScore Rank: Q1: #82/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.647
  • SCImago Journal Rank (SJR): 0.781
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Spandidos Publications style
Li Q, Wei L, Lin S, Chen Y, Lin J and Peng J: Synergistic effect of kaempferol and 5‑fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway. Mol Med Rep 20: 728-734, 2019.
APA
Li, Q., Wei, L., Lin, S., Chen, Y., Lin, J., & Peng, J. (2019). Synergistic effect of kaempferol and 5‑fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway. Molecular Medicine Reports, 20, 728-734. https://doi.org/10.3892/mmr.2019.10296
MLA
Li, Q., Wei, L., Lin, S., Chen, Y., Lin, J., Peng, J."Synergistic effect of kaempferol and 5‑fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway". Molecular Medicine Reports 20.1 (2019): 728-734.
Chicago
Li, Q., Wei, L., Lin, S., Chen, Y., Lin, J., Peng, J."Synergistic effect of kaempferol and 5‑fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway". Molecular Medicine Reports 20, no. 1 (2019): 728-734. https://doi.org/10.3892/mmr.2019.10296