中药功劳木提取物对肿瘤MDR的逆转作用

目的:研究中药功劳木的4种不同工艺提取物逆转肿瘤多药耐药性(multidrug resistance,MDR)的作用,以开发新型的肿瘤MDR逆转剂。方法:采用MTT法检测4种提取物的细胞毒性及其对阿霉素(adriamycin,ADM)的增敏效果;罗丹明123(Rhodamine123,Rh123)蓄积实验检测4种提取物对细胞内药物浓度及P-糖蛋白(P-glycoprotein,P-gp)功能的影响;流式细胞仪检测4种提取物对耐药肿瘤细胞凋亡的影响。结果:10 mg/L为4种提取物的无毒剂量;在此剂量下,4种提取物对K562/ADM细胞逆转倍数分别为Ⅰ-4.81倍,Ⅱ-2.31倍,Ⅲ-4.17倍,Ⅳ-2.39倍,对MCF-7/ADM细胞的逆转倍数分别为Ⅰ-1.82倍,Ⅱ-1.40倍,Ⅲ-2.54倍,Ⅳ-1.51倍;此剂量的4种提取物应用后,使K562/ADM细胞凋亡率分别增加了Ⅰ-13.27%、Ⅱ-7.03%、Ⅲ-20.24%、Ⅳ-11.75%,使MCF-7/ADM细胞凋亡率分别增加了Ⅰ-6.3%、Ⅱ-3.67%、Ⅲ-8.6%、Ⅳ-3.48%。结论:中药功劳木的4种不同工艺提取物能够不同程度的逆转肿瘤细胞的MDR,抑制肿瘤细胞膜上P-gp的“药泵”功能,增加耐药细胞内药物浓度,有望成为肿瘤多药耐药逆转剂的候选药物。

Reversal Effect of Compounds Extracted from Caulis Mahoniae on Tumor Multidrug Resistance

Objective: This study was to research reversal effect of four compounds extracted from Caulis Mahoniae,a traditional Chinese herb,according to different technologies on multidrug resistance(MDR) tumour cells to empolder new reversal agents.Methods: MTT assay was used to determine the cytotoxicity of four compounds alone and four compounds combined with adriamycin(ADM) on human leukemia and breast cancer multidrug resistance cells.Rhodamine 123 accumulation experiment was used to determine the effect of four compounds on intracellular chemotherapy drugs accumulation and P-glycoprotein(P-gp) function.Apoptosis rate of MDR tumor cells were analyzed by Flow cytometer.Results: Inhibitory rates of 10mg/L four compounds for MDR tumou cells were under 10%,so this concentration was as innocuous dosage of four compounds.At this dosage,reversal fold of four compounds on K562/ADM cells was respectivelyⅠ-4.81,Ⅱ-2.31,Ⅲ-4.17,Ⅳ-2.39,and that of four compounds on MCF-7/ADM cells was respectivelyⅠ-1.82,Ⅱ-1.40,Ⅲ-2.54,Ⅳ-1.51.Four compounds of this dosage respectively made intracellular Rh123 concentrations increase Ⅰ-56.13%、Ⅱ-15.01%、Ⅲ-53.52%、Ⅳ-42.21% in K562/ADM cells,and made intracellular Rh123 concentrations increase Ⅰ-64.57%、Ⅱ-21.29%、Ⅲ-59.94%、Ⅳ-59.32% in MCF-7/ADM cells.Four compounds made apoptosis rate of K562/ADM cells increase Ⅰ-13.27%、Ⅱ-7.03%、Ⅲ-20.24%、Ⅳ-11.75%,reapectively.Four compounds made apoptosis rate of MCF-7/ADM cells increase Ⅰ-6.3%、Ⅱ-3.67%、Ⅲ-8.6%、Ⅳ-3.48%,respectively.Conclusion: Four compounds extracted from Caulis Mahoniae according to different technologies could reverse multidrug resistance of tumor cells at different degree,and cound inhibite the "bump" funtion of P-gp on tumor cells membrane and consequently make incellular drugs concentration increased.They would become candidate of tumor multidrug resistance reversal agents.