负载紫杉醇的聚乳酸纳米纤维对宫颈癌的抑制作用

从细胞水平和动物模型两个层次上研究了负载紫杉醇的聚乳酸纤维毡诱导U14宫颈癌细胞凋亡和抑制小鼠U14皮下移植瘤生长的能力.将U14细胞在纤维毡存在下孵育48 h,经Annexin V-FITC及PI双染后行流式细胞分析.结果表明,载药纤维(折合紫杉醇浓度40)g/mL)组总凋亡细胞比例(25.6%)明显高于对照组(1.0%)和未载药纤维组(1.5%).建立U14宫颈癌皮下移植瘤小鼠模型,将其随机分为3组.A组为对照组,不做任何处理.B、C组小鼠以纳米纤维毡覆盖于肿瘤表面,覆盖率约为70%～75%.其中B组纤维毡为纳米聚乳酸电纺丝纤维,不载药,C组为同种材料纤维毡,载有33 wt%紫杉醇.经处理后第7、14天每组各处死动物5～7只,剥离肿瘤,照相,称重,计算抑瘤率.结果表明,载药纤维对U14宫颈癌皮下移植瘤有明显抑制作用(48%～56%).用未载药聚乳酸纤维包裹肿瘤表面,肿瘤质量与对照组无显著差别,说明聚乳酸纤维本身对肿瘤没有抑制作用,载药纤维组所观察到的抑瘤效果为紫杉醇从纤维毡中释放所致.

INHIBITORY EFFECTS OF PACLITAXEL-LOADED PLA NANOFIBERS AGAINST MICE CERVICAL CANCERS

To verify the feasibility of using drug-loaded ultrafine fibers in local chemotherapy of cancers,ability of the paclitaxel(PTX)-loaded polylactide(PLA) fiber mats to induce cell apoptosis of U14 cervical cancer cells and to inhibit the growth of the xenograft U14 cervical cancers was examined.The U14 cells were incubated for 48 h in the presence of the fiber mats,and the cell apoptosis rate(CAR) was evaluated by flow cytometry(FC) with Annexin V-FITC and PI double staining.The FC results showed that after 48 h incubation in the presence of PTX-loaded fibers(equivalent PTX content 40 μg/mL),the total CAR(25.6%) was significantly higher than the control group(1.0%) and the Fiber-only group(1.5%).U14 cervical cancer models were established in balb-c mice.The tumor body was separated from the surrounding tissues and wrapped with nano-fiber mats in a coverage ratio of 70%～75%.Seven and fourteen days after surgery,5～7 animals in each group were sacrificed,and the tumors were separated,cut down,photographed and weighed.The tumor inhibition rates(TIR) were calculated.The results showed that the PTX-loaded(33 wt%) fiber wrapping led to significant inhibition of the growth of U14 cervical cancers(TIR=48%～56%).Although the Fiber-only group animals underwent surgery and their tumors were wrapped with the fiber mats,their tumor weights were not significantly different from those of the Control group,indicating that the PLA fibers themselves did not inhibit the tumor growth,and the inhibitory effects observed in the Fiber-PTX group was due to the released PTX from the fibers.In conclusion,the PTX-loaded PLA fiber mats displayed significant inhibition to the xenograft U14 cervical cancers.They are suitable for local chemotherapy of the U14 cervical cancers before and/or after surgery.