紫花牡荆素对人卵巢癌HO-8910细胞裸鼠移植瘤生长的影响

Effect of casticin on the growth of human ovarian carcinoma HO-8910 cells xenografts in nude mice

目的研究紫花牡荆素(Casticin)对人卵巢癌HO-8910细胞裸鼠移植瘤生长的影响。方法建立人卵巢癌HO-8910细胞裸鼠皮下移植瘤模型,随机分成5组,每组3只:生理盐水组、多西紫杉醇组(0.5mg/kg)、低剂量Casticin组(5mg/kg)、中剂量Casticin组(10mg/kg)和高剂量Casticin组(20mg/kg)。观察各组裸鼠移植瘤生长情况和裸鼠体重的变化;观察裸鼠血清乳酸脱氢酶、谷丙转氨酶、肌酐值和外周血白细胞计数的变化;FCM测定瘤组织细胞凋亡率;Western Blot分析瘤组织细胞凋亡的分子生物学机制。结果 Casticin对移植瘤生长有明显抑制作用,呈剂量和时间依赖性;而对裸鼠体重、谷丙转氨酶、乳酸脱氢酶、肌酐值和外周血白细胞计数均无影响。经Casticin作用16d,裸鼠移植瘤细胞表现出剂量依赖性增加的亚二倍峰,Bcl-2蛋白表达降低,caspase-3蛋白表达增高。结论 Casticin具有抑制人卵巢癌裸鼠移植瘤生长的作用,并通过降低Bcl-2蛋白表达,活化Caspase-3蛋白表达诱导瘤组织细胞凋亡。

【Objective】 To investigate the effect of casticin on the growth of human ovarian carcinoma HO-8910 cells xenografts in nude mice.【Methods】 Models of human ovarian cancer HO-8910 cells xenografts transplanted subcutaneously in nude mice were established,and random divided into five groups： saline group,docetaxel（0.5 mg/kg） group,low dose casticin（5 mg/kg） group,middle dose casticin（10 mg/kg） group and high dose casticin（20 mg/kg） group.Tumor volume,tumor weight and the weight of nude mice were measured.The serum levels of LDH,ALT,Cr and WBC counts were determined.The rate of apoptotic cells of human ovarian carcinoma HO-8910 cells xenografts was analyzed by PI stained FCM.The expressions of bcl-2 protein and caspase-3 protein of HO-8910 cells xenografts were determined by western blot.【Results】 Casticin could significantly suppress the growth of human ovarian carcinoma HO-8910 cells xenografts in nude mice models.There were significant difference in tumor volume and tumor weight between the nude mice treated with casticin of different dose and those treated with normal saline.There were no obvious difference in the weight of nude mice and in the serum levels of LDH,ALT,Cr and WBC counted between the nude mice treated with casticin of different dose and those treated with normal saline.The xenografts cells treated with casticin showed increased cells of sub-G1 population by the flow cytometric analysis in a dose-dependent.Western blot showed that expression of caspase-3 protein was upregulated and protein level of Bcl-2 was depressed after treatment with Casticin in a concentration dependent.【Conclusions】 Casticin suppressed the growth of human ovarian carcinoma HO-8910 cells xenografts in nude mice and induced apoptosis of xenografts cells through downregulation of Bcl-2 expression and activation of caspase-3 expression.