中华胃肠外科杂志
中華胃腸外科雜誌
중화위장외과잡지
CHINESE JOURNAL OF GASTROINTESTINAL SURGERY
2014年
4期
383-387
,共5页
顾钧%李茂岚%吴向嵩%吴文广%张林%丁琦晨%杨佳华%翁昊%丁倩%包润发%束翌俊%刘颖斌
顧鈞%李茂嵐%吳嚮嵩%吳文廣%張林%丁琦晨%楊佳華%翁昊%丁倩%包潤髮%束翌俊%劉穎斌
고균%리무람%오향숭%오문엄%장림%정기신%양가화%옹호%정천%포윤발%속익준%류영빈
胃肿瘤%氟尿嘧啶%聚乳酸%体外杀伤效应
胃腫瘤%氟尿嘧啶%聚乳痠%體外殺傷效應
위종류%불뇨밀정%취유산%체외살상효응
Stomach neoplasms%Fluorouracil%Poly-L-lactic acid%Anti-tumor effects
目的：制备荷载氟尿嘧啶（5-FU）的聚乳酸（PLLA）碳纳米管（CNT）复合材料（5-FU-PLLA-CNTs），并探讨其对人胃癌细胞株（MGC803和MNK45）的体外杀伤效应。方法以PLLA-CNTs为原料，采用超声乳化法荷载5-FU；通过扫描电子显微镜观察5-FU-PLLA-CNTs形态和结构；用紫外可见光光度仪测定不同时间5-FU-PLLA-CNTs的5-FU释放量及累计释放量，并绘制体外释放曲线；设计实验组（不同浓度的5-FU-PLLA-CNTs）及阳性（相应浓度的5-FU）和阴性对照组（不加任何药物），用CCK8法检测不同浓度的5-FU-PLLA-CNTs对MGC803和MNK45的增殖抑制作用；流式细胞术检测5-FU-PLLA-CNTs作用前后细胞凋亡的变化。结果成功制备5-FU-PLLA-CNTs药物深层薄膜，薄膜载药率为（4.54±0.43）%，包封率（21.56±2.36）%。体外释放实验显示，5-FU-PLLA-CNTs在24 h内释放率为23．9％，呈缓慢上升趋势，至31 d体外累计释放率达85．3％。CCK8实验显示，与对照组比较，5-FU-PLLA-CNTs对两株胃癌细胞具有明显抑制作用（P＜0．01），随着药物浓度的增加，抑制作用增强；随着作用时间的延长，呈持续抑制状态。流式细胞仪显示，经1 mg/孔5-FU-PLLA-CNTs处理的实验组MGC803和MNK45细胞凋亡率与阴性对照组比较，差异具有统计学意义（均P＜0．05）；与阳性对照组比较，差异无统计学意义（均P＞0．05）。结论5-FU-PLLA-CNTs具有良好的药物缓释性能，对胃癌细胞株具有明显的杀伤和抑制增殖作用，其最佳浓度为1 mg/孔。
目的：製備荷載氟尿嘧啶（5-FU）的聚乳痠（PLLA）碳納米管（CNT）複閤材料（5-FU-PLLA-CNTs），併探討其對人胃癌細胞株（MGC803和MNK45）的體外殺傷效應。方法以PLLA-CNTs為原料，採用超聲乳化法荷載5-FU；通過掃描電子顯微鏡觀察5-FU-PLLA-CNTs形態和結構；用紫外可見光光度儀測定不同時間5-FU-PLLA-CNTs的5-FU釋放量及纍計釋放量，併繪製體外釋放麯線；設計實驗組（不同濃度的5-FU-PLLA-CNTs）及暘性（相應濃度的5-FU）和陰性對照組（不加任何藥物），用CCK8法檢測不同濃度的5-FU-PLLA-CNTs對MGC803和MNK45的增殖抑製作用；流式細胞術檢測5-FU-PLLA-CNTs作用前後細胞凋亡的變化。結果成功製備5-FU-PLLA-CNTs藥物深層薄膜，薄膜載藥率為（4.54±0.43）%，包封率（21.56±2.36）%。體外釋放實驗顯示，5-FU-PLLA-CNTs在24 h內釋放率為23．9％，呈緩慢上升趨勢，至31 d體外纍計釋放率達85．3％。CCK8實驗顯示，與對照組比較，5-FU-PLLA-CNTs對兩株胃癌細胞具有明顯抑製作用（P＜0．01），隨著藥物濃度的增加，抑製作用增彊；隨著作用時間的延長，呈持續抑製狀態。流式細胞儀顯示，經1 mg/孔5-FU-PLLA-CNTs處理的實驗組MGC803和MNK45細胞凋亡率與陰性對照組比較，差異具有統計學意義（均P＜0．05）；與暘性對照組比較，差異無統計學意義（均P＞0．05）。結論5-FU-PLLA-CNTs具有良好的藥物緩釋性能，對胃癌細胞株具有明顯的殺傷和抑製增殖作用，其最佳濃度為1 mg/孔。
목적：제비하재불뇨밀정（5-FU）적취유산（PLLA）탄납미관（CNT）복합재료（5-FU-PLLA-CNTs），병탐토기대인위암세포주（MGC803화MNK45）적체외살상효응。방법이PLLA-CNTs위원료，채용초성유화법하재5-FU；통과소묘전자현미경관찰5-FU-PLLA-CNTs형태화결구；용자외가견광광도의측정불동시간5-FU-PLLA-CNTs적5-FU석방량급루계석방량，병회제체외석방곡선；설계실험조（불동농도적5-FU-PLLA-CNTs）급양성（상응농도적5-FU）화음성대조조（불가임하약물），용CCK8법검측불동농도적5-FU-PLLA-CNTs대MGC803화MNK45적증식억제작용；류식세포술검측5-FU-PLLA-CNTs작용전후세포조망적변화。결과성공제비5-FU-PLLA-CNTs약물심층박막，박막재약솔위（4.54±0.43）%，포봉솔（21.56±2.36）%。체외석방실험현시，5-FU-PLLA-CNTs재24 h내석방솔위23．9％，정완만상승추세，지31 d체외루계석방솔체85．3％。CCK8실험현시，여대조조비교，5-FU-PLLA-CNTs대량주위암세포구유명현억제작용（P＜0．01），수착약물농도적증가，억제작용증강；수착작용시간적연장，정지속억제상태。류식세포의현시，경1 mg/공5-FU-PLLA-CNTs처리적실험조MGC803화MNK45세포조망솔여음성대조조비교，차이구유통계학의의（균P＜0．05）；여양성대조조비교，차이무통계학의의（균P＞0．05）。결론5-FU-PLLA-CNTs구유량호적약물완석성능，대위암세포주구유명현적살상화억제증식작용，기최가농도위1 mg/공。
Objective To prepare cisPLLAtin-loaded polylactic acid/cnts , and to study the anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines (MGC803 and MNK45). Methods 5-FU-PLLA-CNTs were prepared with ultrasound emulsification. The morphology of 5-FU-PLLA-CNTs was determined by scanning electron microscope (SEM), and its drug loading and drug release curve in vitro were detected by UV-Vis-NIR spectrophotometer. Cells were divided into experiment, positive control and negative control groups. CCK8 method was used to test the cytotoxic effect of 5-FU-PLLA-CNTs in different concentrations on MGC803 and MNK45 cell proliferation. Flow cytometry was employed to measure the apoptotic rate of MGC803 and MNK45 cells before and after the intervention of 5-FU-PLLA-CNTs. Results Deep layer film of 5-FU-PLLA-CNTs was successfully established, whose drug-load rate was (4.54 ±0.43)%, entrapment rate was (21.56 ±2.36)%. In vitro release test showed release rate within 24 h of 5-FU-PLLA-CNTs was 23.9% in a aslowly increasing manner, and accumulating release rate was 85.3% at day 31. CCk8 experiment revealed , as compared to control group, 5-FU-PLLA-CNTs significantly inhibited the proliferation of two cell lines in dose-dependent and time-dependent manner. The best 5-FU-PLLA-CNTs concentration of inhibition for human gastric cancer cell lines was 1 mg/well. Flow cytometry indicated the apoptotic rate of MGC803 and MNK45 cells in experiment group treated by 1 mg/well 5-FU-PLLA-CNTs significantly increased as compared to negative control group (P<0.05), while the difference was not significant as compared to positive control group (P>0.05). Conclusion The 5-FU-PLLA-CNTs has good drug sustained-release capacity, and can significantly kill and inhibit the proliferation of MGC803 and MNK45 cell lines.
