双氢青蒿素抗乳腺癌MDA-MB-231细胞裸鼠移植瘤作用实验研究

Antitumor effect and mechanism of dihydroartemisinin on breast cancer in nude mice with transplanted tumor of human MDA-MB-231 cells

目的研究双氢青蒿素(alpha-Dihydroartemisinin,DHA)对人乳腺癌MDA-MB-231细胞裸鼠移植瘤的抗瘤作用。方法将裸鼠随机分为阴性对照组、DHA低剂量组(DHA给药剂量为50 mg·kg-1·d-1)、DHA中剂量组(DHA给药剂量为100 mg·kg-1·d-1)和DHA高剂量组(DHA给药剂量为200 mg·kg-1·d-1),建立人乳腺癌MDA-MB-231细胞裸鼠移植瘤模型,测定不同浓度的DHA对裸鼠的体重、抑瘤率、胸腺指数、脾脏指数的影响,免疫组化检测移植瘤P53蛋白的表达。结果 DHA可明显抑制移植瘤的生长,DHA低剂量、中剂量和高剂量对移植瘤的抑制率分别为20.25%、31.01%和46.20%,DHA各组胸腺指数和脾脏指数较阴性对照组均有不同的的提高,与阴性对照组比较,DHA高、中剂量组小鼠胸腺指数和脾脏指数均有显著性差异(P<0.05);免疫组化结果显示DHA可下调移植瘤细胞P53蛋白的表达。结论 DHA对人乳腺癌MDA-MB-231细胞移植瘤有显著的抑制作用,其抗癌机理可能是调节机体免疫和下调P53蛋白的表达。

Objective To observe the antitumor effect and mechanism of dibydroartemisinin on breast cancer in nude mice with trans- planted tumor of human MDA-MB-231 cells. Methods The nude mice were randomized into 4 groups：the negative control group, DHA low dose group, DHA middle dose group and DHA high dose group, then nude mice model was established with transplanted tumor of hu- man MDA-MB-231 cells. Different concentrations of DHA were used in nude mice with transplanted tumor of human MDA-MB-231 cells, whose effects on mice weight, inhibition rate of tumor, thymus index and spleen index were determined, and the expression of p53 protein was detected by immunohistochemical staining. Results Transplanted tumor inhibition rates in DHA low dose, middle dose and high dose groups were 20.25% ,31.01% and 46.20% respectively. The thymus index and spleen index of DHA group were improved, the thymus index and spleen index in the high and middle dose groups were significantly different compared with negative control group . Conclusion DHA could significantly inhibit the growth of transplanted tumor of human MDA-MB-231 cells,whose mechanism may be through adjusting the body＇ s immunological function and down-regulating the expression of p53 protein.