摘要
目的:评估紫杉醇-乳酸-羟基乙酸共聚物[paclitaxel-poly(lactic-co-glycolic acid),TAX-PLGA]微球行瘤内直接注射对裸鼠Hep-2喉鳞癌移植瘤的疗效。方法:建立荷Hep-2喉鳞癌裸鼠实体瘤模型,分别对模型鼠采取不同的治疗方法,通过观察各实验组肿瘤体积和质量的改变,计算抑瘤率和肿瘤体积三倍增时间(tripling time,TT)。采用免疫组织化学法检测移植瘤微血管密度(microvessel density,MVD)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达。结果:用药21d后,与0.9%氯化钠溶液瘤内注射(intratumoral injec-tion,i.t.)组相比,TAX治疗各组的肿瘤体积和质量均明显下降(P<0.05),TT均明显延长(P<0.01);低剂量TAX-PLGA微球i.t.组的TT明显大于TAX针剂i.t.组和腹腔注射(intraperitoneal injection,i.p.)组(P<0.05);高剂量TAX-PLGA微球i.t.组的TT明显大于其他TAX治疗各组(P<0.01)。TAX针剂i.p.组、TAX针剂i.t.组、低剂量和高剂量TAX-PLGA微球i.t.组的抑瘤率分别为35.99%、39.37%、47.83%和59.90%,PLGA空白微球不影响肿瘤的生长。实验未发现明显的不良反应。TAX治疗各组的MVD计数、bFGF和VEGF表达较氯化钠溶液对照组有不同程度下降(P<0.05),其中TAX-PLGA微球i.t.给药对bFGF的抑制作用更明显,具有更强的抗肿瘤血管新生作用。结论:在肿瘤局部直接注射多聚物缓释系统药物对喉鳞癌的治疗具有一定应用前景。
Objective： To investigate the efficacy of intratumoral injection of paclitaxel-loaded poly （lactic-co-glycolic acid） （PLGA） microspheres on Hep-2 laryngeal squamous cell xenografts in nude mice. Methods： The solid tumor model bearing Hep-2 laryngeal squamous cell carcinoma was established in BALB/c nude mice. The model group was given with different therapies. The tumor size and tumor weight were recorded in all of the experimental groups. The tumor inhibition rate （IR） and tumor volume tripling time （TT） were calculated. The counts of microvessel density （ MVD）, expressions of basic fibroblast growth factor （bFGF） and vascular endothelial growth factor （VEGF） in xenografts were examined by EnvisionTM immunohistological method. Results： Twenty-one days after treatment, the tumor size and tumor weight of the paclitaxel-treated groups were significantly decreased （P 〈 0.05） and the TFs were significantly prolonged （ P 〈 0.01 ） compared with the saline control group. The TY of the group receiving intratumoral injection of paclitaxel PLGA microspheres at a low dose was significantly longer compared with the group receiving intratumoral （ i. t. ） or intraperitoneal（ i. p. ） injection of paclitaxel （ P 〈 0.05 ）. The TT of the group receiving intratumoral injection of paclitaxel microspheres at a high dose was significantly increased compared with the other paclitaxel-treated groups （P 〈0.01 ）. The tumor inhibition rates of paclitaxel intraperitoneal or intratumoral injection groups were 35.99% and 39.37% , respectively; and they were 47.83% and 59.90% for paclitaxel microsphere intratumoral injection groups at low and high doses, respectively. PLGA blank microspheres had no effect on the tumor growth. No significant toxic reactions were observed in the experiment. The counts of MVD and immunoreactivity of bFGF and VEGF in the paclitaxel-treated groups were significantly decreased compared with the saline control group （P 〈 0.05 ）. The intratumoral injection of paclitaxel microspheres markedly reduced bFGF level and showed stronger anti-angiogenic activity in comparison with i. p. and i. t. administration of paclitaxel injection （P 〈 0.01 ）. Conclusion- Direct administration of polymeric drug control release system into local tumor bodies had a foreground for the treatment of laryngeal squamous cell carcinoma.
出处
《肿瘤》
CAS
CSCD
北大核心
2009年第1期5-10,共6页
Tumor
关键词
喉肿瘤
紫杉醇
生物聚合物
注射
病灶内
动物
实验
小鼠
裸
Laryngeal neoplasms
Paclitaxel
Biopolymers
Injections, intralesional
Animals,laboratory
Mice, nude
