重组人血管内皮抑制素不同给药途径联合顺铂对小鼠Lewis肺癌的疗效

doi:10.6040/j.issn.1671-7554.0.2019.055

摘要/Abstract

摘要： 目的观察重组人血管内皮抑制素(恩度)微量泵入和腹腔注射两种方式联合顺铂对小鼠Lewis肺癌的疗效和不良反应。方法建立C57BL/6J小鼠Lewis肺癌移植瘤模型,并随机分为6组:生理盐水组、生理盐水+腹腔植入渗透压泵组、恩度［5 mg/(kg·d),ip］+顺铂组、恩度［10 mg/(kg·d),ip］+顺铂组、恩度［20 mg/(kg·d),ip］+顺铂组、恩度［5 mg/(kg·d),pump］+顺铂组。治疗后,观察小鼠体征和行为特征,监测肿瘤体积。免疫组织化学法测定肿瘤组织微血管密度(MVD),ELISA法测定小鼠血清血管内皮生长因子(VEGF)水平,收集小鼠血液样本进行血常规和生化检查,并测定渗透压泵中恩度的稳定性。结果恩度［5 mg/(kg·d),pump］+顺铂组与生理盐水组、生理盐水+腹腔植入渗透压泵组、恩度［5 mg/(kg·d),ip］+顺铂组、恩度［10 mg/(kg·d),ip］+顺铂组相比,抑瘤率最高,MVD降低,血清中VEGF表达量下降,差异均有统计学意义(P均<0.001);与恩度［20 mg/(kg·d),ip］+顺铂组相比,以上指标差异均无统计学意义(P均>0.05)。与腹腔注射相比,恩度微量泵入并未增加药物不良反应(P>0.05)。恩度在渗透压泵中的稳定性至少维持7 d。结论恩度微量泵入比腹腔注射更加有效地抑制小鼠肿瘤生长,并未增加药物不良反应,同时降低药物使用剂量。

关键词: 小鼠, 肺肿瘤, 重组人血管内皮抑制素, 顺铂, 植入式渗透压泵

Abstract: Objective To observe the efficacy and safety of micro pump and intraperitoneal injection of recombinant human endostatin(endostar)combined with cisplatin on Lewis lung cancer xenografts in mice. Methods Subcutaneous Lewis lung cancer xenografts model of C57BL/6J mice was established, then the mice were randomly divided into six groups, with ten in each group: saline group, saline plus intraperitoneal implantation osmotic pump group, endostar ［5 mg/(kg·d), ip］ plus cisplatin group, endostar ［10 mg/(kg·d), ip］ plus cisplatin group, endostar ［20 mg/(kg·d), ip］ plus cisplatin group and endostar ［5 mg/(kg·d), pump］ plus cisplatin group. After drug administration, the signs and behaviors of the mice were observed dynamically, and the tumor volumes in different groups were measured. The microvascular density(MVD)in xenografts tumor tissues was detected by immunohistochemistry, and the serum vascular endothelial growth factor(VEGF)level was evaluated by ELISA. Blood samples of mice were collected 山东大学学报 (医学版)57卷5期 -王聪,等.重组人血管内皮抑制素不同给药途径联合顺铂对小鼠Lewis肺癌的疗效 \=-for blood routine and biochemical examination, and the stability of endostar in the osmotic pump was detected. Results Compared with saline group, saline plus intraperitoneal implantation osmotic pump group, endostar ［5 mg/(kg·d), ip］ plus cisplatin group and endostar ［10 mg/(kg·d), ip］ plus cisplatin group, endostar ［5 mg/(kg·d), pump］ plus cisplatin group has the higher tumor inhibitory rate, the lower MVD and serum VEGF expression(all P<0.001). There were no statistical differences between tumor inhibitory rate, MVD and the VEGF expression in endostar ［5 mg/(kg·d), pump］ plus cisplatin group and endostar ［20 mg/(kg·d), ip］ plus cisplatin group(all P>0.05). Endostar via micro pump had the same adverse reaction with intraperitoneal injection(P>0.05). Endostar remained stable and active in osmotic pumps for at least 7 days. Conclusion The tumor inhibitory effect of endostar via micro pump is better than intraperitoneal injection on Lewis lung cancer xenografts in mice without increasing drug toxicity and with reducing dosages of drug.

Key words: Mice, Lung cancer, Recombinant human endostatin, Cisplatin, Osmotic pump

中图分类号:

R734.2

王聪,朱玲,万云焱,姚周虹,李德志,许小婷,徐鹏飞,林殿杰. 重组人血管内皮抑制素不同给药途径联合顺铂对小鼠Lewis肺癌的疗效[J]. 山东大学学报 (医学版), 2019, 57(5): 93-98.

WANG Cong, ZHU Ling, WAN Yunyan, YAO Zhouhong, LI Dezhi, XU Xiaoting, XU Pengfei, LIN Dianjie. Therapeutic effect of different administration ways of recombinant human endostatin combined with cisplatin on Lewis lung cancer xenografts in mice[J]. Journal of Shandong University (Health Sciences), 2019, 57(5): 93-98.

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