LyP-1-MWNTs—GEM的制备及其体外靶向抑制人胰腺癌细胞增殖效应的研究

Preparation of LyP-1-conjugated multi-walled carbon nanotubes loaded with gemcitabine and their cytotoxicity on human pancreatic cancer cells in vitro

目的观察LyP-1靶向多壁碳纳米管（LyP-1-MWNTs）携载吉西他滨（GEM）对人胰腺癌细胞的体外杀伤效应。方法共价合成法制备LyP-1MWNTs，采用噻唑蓝（MTF）法检测0．1、1．0、10．0、25．0、50．0、75．0mg／L浓度LyP-1-MWNTs—GEM对淋巴结高转移特性胰腺癌细胞株BxPC-3-LN5作用24、48、72h后生长抑制效应，流式细胞仪检测细胞凋亡率。结果LyP-1-MWNTs—GEM对细胞增殖抑制作用呈浓度和时间依赖性，在50．0、75．0mg／L浓度时，LyP-1-MWNTs—GEM组抑制率均显著高于MWNTs-GEM和GEM组（P〈0．05）；LyP-1-MWNTs—GEM组抑制率时间相关性规律为：72h〉48h〉24h（P〈0．05，除外75．0mg／L时72h比48h）。流式细胞仪测定LyP-1-MWNTs—GEM组细胞凋亡率（28．68％）亦高于MWNTs．GEM（19．79％）和GEM（16．73％）组。结论LyP-1-MWNTs-GEM在一定浓度时能依赖靶向效能显著抑制BxPC-3-LN5细胞增殖，促进其凋亡。

Objective To study the anti-proliferation effects of GEM-loaded LyP-1-conjugated muhi2walled carbon nanotubes （LyP-1-MWNTs） on human pancreatic cancer cells in vitro. Methods LyP-1-MWNTs were prepared by method of covalent conjugation. By methyl thiazol tetrazolium （M3T） as- say, the cytotoxic effects of LyP-1-MWNTs-GEM on human pancreatic cancer cell line BxPC-3-LN5 （ with high metastatic capacity to the lymph nodes） were detected at 0. 1, 1.0, 10.0, 25. 0, 50. 0, 75. 0 mg/L drug concentrations at 24th, 48th and 72nd h respectively. Meanwhile, the apoptosis rate was analyzed by using flow cytometry. Results LyP-1-MWNTs：GEM could obviously inhibit the proliferation of BxPC-3- LN5 cells in a concentration- and time-dependent manner. At the concentrations of 50. 0 and 75. 0 mg/L, the inhibition rate of LyP-1-MWNTs-GEM was significantly higher than that of MWNTs-GEM and GEM at 24th, 48th and 72nd h respectively （ P 〈 0. 05 ）. The time-dependent inhibition rate of LyP-1-MWNTs- GEM was： 72 h 〉48 h 〉24 h （P 〈 0.05, except 72 h vs. 48 h in 75 mg/L）. Flow cytometry revealed that apoptosis ratio of LyP-1-MWNTs-GEM （28.68%） was accordingly higher than that of MWNTs-GEM （ 19. 79% ） and GEM （ 16.73% ）. Conclusion LyP-1-MWNTs-GEM could apparently inhibit the prolifer： ation and promote the apoptosis of BxPC-3-LN5 cells by improving the targeting efficiency.