超声结合聚乙二醇化多西他赛白蛋白纳米粒治疗裸鼠非小细胞肺癌模型疗效观察

Observation on therapeutic efficacy of ultrasound combined with docetaxel loaded PEG-albumin nanoparticles on non-small cell lung cancer model in nude mice

目的利用超声结合聚乙二醇化多西他赛白蛋白纳米粒(PEG-DANPs)治疗裸鼠非小细胞肺癌模型,为临床治疗人非小细胞肺癌提供一种新思路。方法建立BALB/c裸鼠人非小细胞肺癌皮下移植瘤及原位癌模型,分别用多西他赛白蛋白纳米粒(DANPs)、PEG-DANPs及PEG-DANPs结合超声波(US)照射对两组裸鼠进行治疗,单次疗程为7 d,共4个疗程,超声波辐照强度为1 MHz,每次时长30 s。全部疗程给药结束2 d后,将全部造模裸鼠处死,取皮下组瘤块进行TUNEL实验观察癌细胞凋亡情况,对原位癌组裸鼠的肺及肝组织进行HE染色病理实验及病理半定量分析。结果与其他给药组相比,US+PEG-DANPs组裸鼠瘤块体积最小(P<0.05,P<0.01);同时其体重保持最好,提示其毒性最小(P<0.05)。从NSCLC原位癌裸鼠肺组织和肝组织病理图来看,US+PEG-DANPs抑制原位癌、抗转移作用最为明显;对其肺组织和肝组织病理图进行半定量分析,差异有统计学意义(P<0.05)。根据TUNEL法检测结果,US+PEG-DANPs组诱导癌细胞凋亡的能力最强。结论超声波结合PEG-DANPs对裸鼠非小细胞肺癌模型的治疗效果明显,有望成为治疗非小细胞肺癌的一种新选择。

Objective To treat non-small cell lung cancer model in nude mice by ultrasound combined with docetaxel loaded PEG-albumin nanoparticles(PEG-DANPs),so as to provide a new idea for clinical treatment of human non-small cell lung cancer.Methods The models of subcutaneous transplanted tumor and carcinoma in-situ of human non-small cell lung cancer in BALB/c nude mice were established.Docetaxel loaded albumin nanoparticles(DANPs),PEG-DANPs and PEG-DANPs combined with ultrasound(US)were used to treat the two groups of nude mice,with a single course of treatment of 7 days and a total of 4 courses of treatment.The intensity of ultrasound irradiation was 1 MHz and the duration of each time was 30 s.Two days after the administration of the whole course of treatment,all the nude mice were sacrificed,and the tumor mass of the subcutaneous group was taken for TUNEL test to observe the apoptosis of cancer cells.The lung and liver tissues of nude mice of the in-situ cancer group were subjected to pathological experiment of HE staining and semi-quantitative pathological analysis.Results Compared with other groups,the tumor volume of nude mice in the US combined with PEG-DANPs group was the smallest(P<0.05,P<0.01).At the same time,its weight kept the best,suggesting that its toxicity was the smallest(P<0.05).From the pathological images of lung tissue and liver tissue of nude mice with NSCLC carcinoma in-situ,US combined with PEG-DANPS have the most obvious efficacy on inhibiting carcinoma in-situ and resisting metastasis.Semi-quantitative analysis was given to the pathological images of lung and liver,and the difference was statistically significant(P<0.05).According to TUNEL method,the ability of inducing apoptosis of cancer cells in the US combined with PEG-DANPs group was the strongest.Conclusion Ultrasound combined with PEG-DANPs have obvious therapeutic efficacy on non-small cell lung cancer model in nude mice,which is expected to be a new choice for the treatment of non-small cell lung cancer.