Alstonia mairei total alkaloids enhance the sensitivity of colorectal cancer to 5-fluorouracil chemotherapy
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 cyto-toxicity 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 23.71μg/mL,respectively.The tumor inhibition rate of low dose(100mg/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 pro-longed,and the plasma concentration of FUrd was significantly decreased.Conclusion The Alstonia mairei total alka-loids 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.
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