目的研究脂质体-姜黄素水溶制剂抗肝癌效应的稳定性。方法MTT法观察脂质体-姜黄素水溶制剂(放置1、2、4、8、12个月)对Bel-7402细胞增殖的抑制作用。原位末端标记方法(TUNEL技术)观察脂质体-姜黄素水溶制剂放置12个月后诱导Bel-7402细胞凋亡的作用。免疫组织化学染色(SABC)法检测脂质体-姜黄素水溶制剂放置12个月后对Bax、Bcl-2和P53蛋白表达的影响。结果姜黄素水溶制剂随着放置时间的延长,抑制Bel-7402细胞增殖和诱导凋亡的作用均显著减弱。脂质体-姜黄素随放置时间的延长,抑制Bel-7402细胞增殖和诱导凋亡的作用无明显衰减现象,至放置12个月后脂质体-姜黄素10、5及0. 25μg/mL 3个剂量对Bel-7402细胞增殖仍有显著抑制作用,与同质量浓度的姜黄素比较,差异显著(P<0. 01),抑制作用随药物质量浓度增高而有加强趋势,最高抑制率可达43. 90%,且呈量效关系,3个剂量组间差异有显著性(P<0. 01),同质量浓度的脂质体-姜黄素的抑制率显著高于姜黄素的抑制率(P<0. 01)。姜黄素-脂质体放置12个月,Bel-7402细胞凋亡率达63. 7%。结论脂质体能显著提高姜黄素对Bel-7402细胞增殖的抑制和诱导凋亡作用。脂质体-姜黄素水溶制剂放置12个月后对P53表达有显著影响,但对Bax和Bcl-2的表达无显著影响。

Objective To study the stability of anti-liver cancer effects by liposome-curcumin in water solution. Methods Inhibition of liposome-curcurnin in water solution(exposed for l,2,4,8,12 months)on proliferation of Bel-7402 cells was observed by MTT assay,the effect of inducing Bel-7402apoptosis of liposome-eurcumin in water solution for 12 months was observed by end 1abeling method in sltu(TUNEL technique),and the effect of liposome-curcumin in water solution for 12 months on protein expression of apoptosis related gene Bax,Bcl-2,and P53 was observed by immunohistoehemical staining(Strep Avidin-Biotin-enzyme Complex,SABC method). Results Both the effects of inhibited hyperplasia and introdueed apoptosis to Bet-7402 cell by eureumin in water solution were apparently weakened with the time lasting,while the effect had no obvious weakening when it came to liposome-curcumin in water solution,and the three different dosages of liposome cureumin(10,5,and 0. 25 μg/mL)could also cause remarkable effect on inhibition of the proliferation of Bel-7402 even if exposing for 12 months. It differed significantly from the eureumin in water solution in the same density(P<0. 01),and the effect on inhibition of multiplieation had the tendency to strengthen with the density increasing of the medicine. The top inhibitory rate could be up to 43. 90%and present amount-result relation differences among the groups of different dosage,which were significant(P

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[基金项目]

国家自然科学基金资助项目(30271562,30371787);国家科技部重大基础研究资助项目(2002CCC00300);湖北省自然科学基金资助项目(2001ABB171);湖北省教育厅“十五”重大研究项目(2002D00003);湖北省“十五”攻关项目(2002AA301C08)