Journal of Shandong University (Health Sciences) ›› 2024, Vol. 62 ›› Issue (6): 30-37.doi: 10.6040/j.issn.1671-7554.0.2024.0261

• Preclinical Medicine • Previous Articles     Next Articles

Alstonia mairei total alkaloids enhance the sensitivity of colorectal cancer to 5-fluorouracil chemotherapy

WANG Xiao1, KONG Wenru1, CUI Weiliang2, WANG Shuqi1   

  1. 1. School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China;
    2. Shandong Institute for Food and Drug Control, Jinan 250101, Shandong, China
  • Published:2024-07-15

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Abstract: Objective To observe the sensitizing effect of Alstonia mairei total alkaloids on 5-fluorouracil(5-FU)in the treatment of colorectal cancer, and to explore the influence on the pharmacokinetics of 5-FU. Methods The cytotoxicity of Alstonia mairei total alkaloids combined with 5-FU on HCT15 human colorectal adenocarcinoma cells and CT26.WT mouse colon cancer cells was evaluated by CCK-8 kit. A mouse subcutaneous tumor model was established to observe the effects of 5-FU and Alstonia mairei total alkaloids on tumor growth when used alone or in combination. The pharmacokinetic parameters of 5-FU and its metabolites dihydrofluorouracil(FUH2)and fluorodeoxyuridine(FUrd)in rats were determined by LC-MS/MS. Results The IC50 values of Alstonia mairei total alkaloids on HCT15 and CT26.WT cells were 31.98 μg /mL and 23.71 μg /mL, respectively. The tumor inhibition rate of low dose(100 mg/kg)and high dose(200 mg/kg)Alstonia mairei total alkaloids combined with 5-FU in tumor-bearing mice increased from 50.91% to 58.56% and 62.16%, respectively. The T1/2 of 5-FU combined with Alstonia mairei total alkaloids was significantly prolonged, and the plasma concentration of FUrd was significantly decreased. Conclusion The Alstonia mairei total alkaloids have certain cytotoxicity against colorectal cancer cells, and its anti-colorectal cancer activity can be significantly enhanced in combination with 5-FU. Alstonia mairei total alkaloids may enhance the biological activity of 5-FU by reducing the concentration of DPD to delay the catabolism of 5-FU and regulate its anabolic pathway.

Key words: Alstonia mairei, Colorectal cancer, Alkaloids, 5-Fluorouracil, Cytotoxicity

CLC Number: 

  • R574
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