摘要
目的:研究载羟基喜树碱(Hydroxycamptothecin,HCPT)的聚乙二醇-聚谷氨酸苄酯(PEG-PBLG)纳米微球对口腔鳞癌及结肠癌的体内抗瘤作用。方法:采用超透析法制备HCPT/PEG-PBLG纳米胶束,透射电镜观察纳米微球的形态,应用HCPT/PEG-PBLG纳米微球治疗口腔鳞癌或结肠癌裸鼠移植瘤,观察移植瘤的生长状态及组织病理学改变。结果:HCPT/PEG-PBLG纳米微球为核-壳型结构,大小约230nm;于对照组比较,所有HCPT治疗组均可明显抑制口腔鳞癌或结肠癌移植瘤的生长(P<0.01),其中HCPT/PEG-PBLG纳米微球组的抑瘤率明显高于HCPT组(P<0.01),PEG-PBLG组对移植瘤的生长无抑制作用(P>0.05);对口腔鳞癌移植瘤的抑瘤率分别为69.6%(HCPT,3mg/kg,qd)、74.1%(HCPT,10mg/kg,qd)、59.8%(HCPT,3mg/kg,qod)和85.6%(HCPT/PEG-PBLG3mg/kg,qod);对结肠癌移植瘤的抑瘤率分别为70.0%(HCPT,3mg/kg,qod)和83.8%(HCPT/PEG-PBLG3mg/kg,qod)。组织病理学显示:PEG-PBLG、HCPT/PEG-PBLG组肿瘤细胞可见较多吞噬小体,而HCPT组未见;HCPT、HCPT/PEG-PBLG组肿瘤细胞可见较多凋亡和坏死。结论:HCPT/PEG-PBLG纳米微球可明显提高HCPT的抑瘤作用,PEG-PBLG纳米微球可成为HCPT类药物的理想新型载体。
Objective: To investigate the antitumor effect of hydroxycamptothecin (HCPT) loaded nanosphere made from poly(ethylene glycol)-poly (-benzyl-L- glutamate)(PEG-PBLG) in the treatment of oral squamous cell carcinoma or colon cancer. Methods: HCPT/PEG-PBLG nanosphere was prepared by the diafitration method. Transmission electron microscope (TEM) was used to observe the shape of nanosphere, Xenografts of oral squamous cell carcinoma (Tca8113 cell line) or colon cancer (Lovo cell line) implanted in BALB/c nude mice were treated with HCPT/PEG-PBLG nanosphere. The growth state and histopathological changes of Tca8113 cells xenografts or Lovo cells xenografts were observed and the tumor doubling times and inhibition rate were calculated. Results: The shape of HCPT/ PEG-PBLG nanosphere was a core-shell structure and the nanosphere size was about 230 nm, with 200 nm in core diameter and 30 nm in shell thickness. Compared with the control group, Tca8113 cells xenografts or Lovo cells xenografts in all HCPT-treated group grew slowly and tumor doubling times prolonged(P〈0,01), The tumor inhibition rate of HCPT/PEG-PBLG nanosphere treated group was significant higher than that of HCPT treated group (P〈0.01). There was no any tumor inhibition effect of PEG-PBLG treated group (P〉0.05). The xenografts inhibition rate for oral squamous cell carcinoma was 69.6% (HCPT 3mg/kg/qd),74.1% (HCPT 10 mg/kg/qd), 59.8% (HCPT 3 mg/kg/qod) and 85.6% (HCPT/PEG-PBLG 3 mg/kg/qod), respectively. The xenografts inhibition rate for colon cancer was 70.0% (HCPT 3mg/kg/qod) and 83.8% (HCPT/PEG-PBLG 3 mg/kg/qod). The histopathology showed that there were many phagosomes inside tumor cells in PEG-PBLG or HCPT/PEG-PBLG treated group, but there was no phagosome inside tumor cells in HCPT treated group under TEM. There were many apoptotic cells and necrotic area in HCPT or HCPT/PEG-PBLG treated group. Conclusion: HCPT/ PEG-PBLG nanosphere could enhance the antitumor effect of HCPT and PEG-PBLG nanosphere would be an ideal vector for drug analogous to HCPT.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2006年第9期527-530,共4页
Chinese Journal of Clinical Oncology
基金
广东省科技计划项目(编号:2003C50113)l
广东省自然科学基金资助(编号:021865)
关键词
聚乙二醇
聚谷氨酸苄酯
载药纳米胶束
羟基喜树碱
移植瘤
口腔鳞癌
结肠癌
Poly(ethylene glycol) Poly(-benzyl-L-glutamate) Drug loaded nanosphere Hydroxycamptothecin Xenografts Oral squamous cell carcinoma Colon cancer