摘要
目的探讨改良闭环羟基喜树碱(HCPT)药用剂型体外抑制口腔鳞癌细胞株的疗效。方法透析法制备载闭环羟基喜树碱/聚乙二醇-聚谷氨酸苄酯(HCPT/PEG-PBLG)纳米微球,与HCPT羧酸钠盐分别作用于Tca8113细胞,对比观察细胞形态学改变,MTT检测细胞毒作用,流式细胞仪、DNA凝胶电泳检测细胞周期变化及细胞凋亡。结果成功制备HCPT/PEG-PBLG纳米微球,包封率56.8%;载药率7.5%。Tca8113细胞经HCPT和HCPT/PEG-PBLG分别作用后,显微镜形态学观察见细胞凋亡、生长抑制。MTT检测显示HCPT呈现明显细胞毒作用;HCPT纳米微球剂型组48h时生长抑制率低于HCPT普通剂型组(P≤0.01),至96h时则与HCPT普通剂型组差异已无统计学意义(P>0.05)。流式细胞仪、DNA凝胶电泳检测细胞周期发生变化:HCPT阻抑细胞于S期,同时诱导细胞凋亡;HCPT/PEG-PBLG组细胞周期与HCPT组改变类似,但S期阻抑增加速度平缓,慢于后者。结论HCPT对Tca8113细胞具有较强的抑瘤作用,阻抑细胞周期于S期并诱导细胞凋亡。HCPT纳米微球剂型具有药物缓释优点,体外实验作用平缓,终末抑瘤效果与HCPT羧酸钠盐剂型持平。
Objective To improve the pharmaceutical dosage form of Hydroxycamptothecine （HCPT） and to explore its suppressive effects and inhibitive mechanism on tongue squamous cell carcinoma Tca8113 cell line in vitro. Methods The closed ring form HCPT-loaded PEG-PBLG nanoparticles were synthesized and tested. After affected by HCPT and HCPT/PEG-PBLG respectively in vitro, Tca8113 cells＇ morphologic changes were observed, cytotoxicity effects were evaluated by MTT assay, the cell cycle and apoptosis changes were assessed with flow cytometry （FCM） and DNA gel electrophoresis. Results HCPT/PEG-PBLG nanoparticles had been successfully synthesized, with 56.8% in encapsulation efficiency and 7.5% in loading level. Tca8113 cells suppression and apoptosis were observed both in HCPT and HCPT/PEG-PBLG group under microscope. Results of MTT assay showed that HCPT had been obvious toxic to Tca8113 cells. HCPT/PEG-PBLG showed similar effectiveness but relatively delayed at check point to that of HCPT： GI value was less than that of HCPT at 48 hours （P〈0.01） and equal to HCVF at 96 hours （no statistical significance was found） （P 〉 0.05）. FCM detected cell cycle variation： in HCPT groups, cells had been retarded in S phase and apoptosis rate raised. Compared with HCPT, HCPT/PEG-PBLG had similar effects while the velocity of the effectiveness was slow. DNA extraction and gel electrophoresis demonstrated classical DNA ladder mark of apoptosis induced by HCPT and HCPT/PEG-PBLG. Conclusion HCPT appeared to fairly restrained tumor growth of Tca8113 cell in vitro： delayed cell cycle in S phase and induced apoptosis. HCPT/ PEG-PBLG nanoparticles slowed down the drug release. So, compared wih HCPT, it showed more slight reactions and achieved the same final anti-tumor effects.
出处
《中华口腔医学研究杂志（电子版）》
CAS
2009年第3期16-20,共5页
Chinese Journal of Stomatological Research(Electronic Edition)
基金
广东省国际合作科技项目基金(2003C50113)
广东省科技计划项目基金(2007B031516010)
关键词
羟基喜树碱
聚乙二醇
聚谷氨酸苄酯
口腔鳞状细胞癌
纳米微球
Hydroxycamptothecine （HCPT）
Poly [ethylene glycol] （PEG）
Poly [γ-benzyl- L-glutamate]（PBLG）
Oral Squamous Cell Carcinoma（OSCC）
Nanoparticles
