摘要
目的研究丹皮酚(paeonol,Pae)在体内外对人食管癌细胞Eca-109的抑瘤作用及其对细胞凋亡的影响。方法采用噻唑蓝(MTT)体外试验法和灌胃给药体内抗肿瘤试验。光镜及电镜观察各组的肿瘤组织的形态学变化。应用末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)法测定细胞凋亡指数。结果丹皮酚在体外对Eca-109细胞有明显的细胞毒作用,半数抑制浓度(IC50)为0.342mmol·L-1;体内灌胃给予丹皮酚25、50、100和200mg·kg-1对裸鼠移植人食管癌Eca-109的抑制率分别为10.67%、23.54%、27.91%和34.46%;顺铂5mg·kg-1组抑瘤率为58.71%;丹皮酚在100mg·kg-1剂量下与顺铂5mg·kg-1联合用药抑制率为77.91%。光镜下用药组可见较多凋亡的肿瘤细胞。透射电镜下可见肿瘤细胞核染色质浓缩边聚、胞质浓缩、核碎裂以及凋亡小体形成等典型的凋亡表现。用药组凋亡指数较对照组明显增加。结论丹皮酚在体内外具有抑制人食管癌Eca-109细胞增殖及诱导其凋亡作用。
Aim To investigate the inhibitory effect of paeonol (Pae) on the human esophageal cancer cell line Eca-109 in vitro and in vivo and its effect on apoptosis. Methods Cytotoxic effect of Pae on Eca-109 cells cultured in vitro was measured by MTT assay. Anti-tumor activity was performed on BALB/c n xenografts model. The morphologic changes ude mice of tumor tissue were observed under light microscope and transmission electron microscope. The apoptosis index was assessed by TUNEL. Results Pae had significant inhibitory effect on the proliferation of Eca-109 cells, and the IC50 value was 0. 342 mmol·L^-1. In the model of human esophageal cancer xenografts in BALB/c nude mice,the inhibitory rates of Pae group (25,50,100, 200 mg ·kg^-1 ) were 10. 67% ,23.54% ,27.91% and 34. 46% respectively. In vivo administration of Pae 100 mg ·kg^-1 combined with cisplatin 5mg ·kg^-1 resulted in a significant inhibition of Eca-109 tumor growth with the inhibitory rate of 77.91%, compared with cisplatin used alone (58. 71% ). The more apoptotic tumor cells could be seen under light microscope in every theraperutic groups than those in control. Changes of uhrastructure of tumor cells including concentration and side accumulation of the nuclear chromatin, and the fragmentation of the nuclear was observed under transmission electronic microscope. Apoptosis body was also found. The apoptosis indexes of every theraperutic groups were significantly different from the control. Conclusion Pae can inhibit the cell growth and induce apoptosis in human esophageal cancer cell line Eca-109 in vitro and in vivo.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第5期654-658,共5页
Chinese Pharmacological Bulletin
基金
安徽省自然科学基金资助项目(No050430901)
安徽省科技厅年度重点资助项目(No05023090)