2. Academic Validation
  3. Ginsenoside Rg3 enhances the anticancer effects of 5-fluorouracil in colorectal cancer and reduces drug resistance and the Hedgehog pathway activation

Ginsenoside Rg3 enhances the anticancer effects of 5-fluorouracil in colorectal cancer and reduces drug resistance and the Hedgehog pathway activation

  • Arab J Gastroenterol. 2024 Nov 4:S1687-1979(24)00101-1. doi: 10.1016/j.ajg.2024.09.003.
Xiaoqian Bu 1,  Huizhi Feng 2,  Zhengzheng Yan 3
Affiliations

Affiliations

  • 1 Department of Cancer Center, Shanxi Bethune Hospital, Taiyuan 030032, Shanxi Province, China.
  • 2 Department of Gastroenterology, Shanxi Cancer Hospital, Taiyuan 030013, Shanxi Province, China.
  • 3 Department of General Surgery, Shanxi Bethune Hospital, Taiyuan 030032, Shanxi Province, China. Electronic address: Yanzhengzheng6518@163.com.
PMID: 39500672 DOI: 10.1016/j.ajg.2024.09.003
Abstract

Background and study aims: This study aimed to ascertain the inhibitory effect of ginsenoside Rg3 (Rg3) combined with 5-fluorouracil (5-FU) on 5-FU-resistant cells HCT116/5-FU and its molecular mechanism.

Material and methods: The HCT116 cell line resistant to 5-FU (HCT116/5-FU) was established by repeated exposure to gradually increasing 5-FU concentrations. The effects of different concentrations of Rg3 and 5-FU on colorectal Cancer (CRC) cell proliferation were evaluated, and suitable concentrations were screened for subsequent experiments. The treatment efficacy of Rg3 and 5-FU alone and in combination with CRC cell activity was observed, and the inhibitory effect of Rg3 and 5-FU on the Hedgehog pathway was verified. Finally, the effects of Rg3 and 5-Fu on in vivo tumor formation were evaluated in vivo.

Results: Rg3 enhanced the therapeutic efficacy of 5-FU in HCT116 cells by inducing Apoptosis and suppressing cell activities and epithelial-mesenchymal transition (EMT), showing strong anti-tumor effects. Rg3 enhances the chemosensitivity of drug-resistant HCT116/5-FU cells to 5-FU. Additionally, the expression of Hedgehog pathway-relevant proteins (PTCH1, PTCH2, GLI1, and SHH) was increased in drug-resistant HCT116/5-FU cells, and Rg3 and 5-FU co-treatment downregulated the expression of PTCH1, PTCH2, GLI1, and SHH proteins in HCT116/5-FU cells. Rg3 reversed 5-FU resistance via by modulating the Hedgehog pathway. Rg3, in combination with 5-FU, repressed human CRC xenograft growth in nude mice, suppressed the expression of the proliferative nuclear factor KI67 in tumors, and promoted Apoptosis.

Conclusion: Rg3 enhances the Anticancer effects of 5-FU in CRC cells that are sensitive and resistant to 5-FU, and its mechanism of action may be related to the inhibition of Hedgehog pathway activation.

Keywords

5-fluorouracil; Colorectal cancer; Ginsenoside Rg3; Invasion; Migration.

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