双氢青蒿素对人卵巢癌细胞株HO-8910裸鼠皮下移植瘤的生长及Caspase-3活性的影响

目的 探讨双氢青蒿素(DHA)对人卵巢癌细胞株HO-8910裸鼠皮下移植瘤的生长及Caspase-3活性的影响.方法 建立人卵巢癌裸鼠皮下移植瘤模型,随机分为双氢青蒿素低、高剂量组、生理盐水组及阳性对照顺铂(DDP)组,每组5只,用药前后分别称取裸鼠体重,绘制体重变化曲线;DDP组连续腹腔注射10 d,其他三组分别灌胃连续给药10 d,停药后24 h后处死裸鼠,称取瘤质量,计算抑瘤率,免疫组化检测Caspase-3的阳性表达率.结果 低、高剂量DHA组及DDP组抑瘤率分别为30.00%,48.03%及60.06%.四组间瘤重比较,差异均有统计学意义(P<0.05);低剂量DHA组与DDP组、高剂量DHA组比较,差异有统计学意义(P<0.008 3);高剂量DHA组与DDP组比较,差异无统计学意义(P=0.04).免疫组化检测各组Caspase-3的阳性表达时,NS组、低、高剂量DHA组和DDP组的阳性表达率分别为18%,29%,73%,80%,随着青蒿素剂量的增加,Caspase-3活性逐渐增加,高剂量DHA组与DDP组比较差异无统计学意义(P＞0.01),而其他各组间两两比较,差异均有统计学意义.结论 双氢青蒿素对人卵巢癌细胞株HO-8910裸鼠皮下移植瘤有明显的抑制作用,在体内可能通过活化Caspase-3诱导细胞凋亡而发挥抗肿瘤作用.

Influence of dihydroartemisin on the activity of Caspase-3 and the growth of human ovarian cancer cell line HO-8910 transplanted tumor under the skin of nude mice

Objective To explore the influence of dihydroartemisin(DHA) on the activity of Caspase-3 and the growth of human ovarian cancer cell line HO-8910 transplanted tumor under the skin of nude mice.Methods The transplanted human ovarian carcinoma model was established by the subcutaneous injection of HO-8910 cells under the skin of nude mice,and then the mice were randomly divided into low dose group of DHA,high dose group of DHA,saline group,DDP positive control group.The nude mice were weighed before and after taking medicine,and the curves of weight was made.The mice in DDP group were continuously intraperitoneally injected with DDP for 10 d,and were gavaged for 10 d in the other three groups.The nude mice were killed 24 h after the last medication.The transplanted tumor was weighed and the inhibitive rate was calculated.Immunohistochemistry method was used to detect the positive rate of Caspase-3.Results The inhibitive rates in low and high dose groups and DDP group were 30.00%,48.03%,and 60.06%,respectively.The tumor weight were significantly different among 4 groups(P<0.05),and significantly lower in low dose group than those in high dose group and DDP group(P<0.008 3).Immunohistochemistry results showed that the positive rates of Caspase-3 in saline group,low and high dose groups and DDP group were 18%,29%,73% and 80%,respectively.There was statistical difference in expression of Caspase-3 between four groups except between high dose group and DDP group.Conclusion Dihydroartemisin can inhibit the growth of tumor in human ovarian cancer cell line Ho-8910 transplanted nude mice through activating the Caspase-3 activity and inducing the cell apoptosis.