Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (5): 93-98.doi: 10.6040/j.issn.1671-7554.0.2019.055

Previous Articles    

Therapeutic effect of different administration ways of recombinant human endostatin combined with cisplatin on Lewis lung cancer xenografts in mice

WANG Cong1, ZHU Ling1, WAN Yunyan1, YAO Zhouhong1, LI Dezhi1, XU Xiaoting2, XU Pengfei1, LIN Dianjie1   

  1. 1. Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China;
    2. Department of Respiratory Medicine, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, Fujian, China
  • Published:2022-09-27

PDF (PC)

104

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

CLC Number: 

  • R734.2
[1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[2] 张仁锋, 张岩, 温丰标, 等. 6058例肺癌患者病理类型和临床流行病学特征的分析[J]. 中国肺癌杂志, 2016, 19(3): 129-135. ZHANG Renfeng, ZHANG Yan, WEN Fengbiao, et al. Analysis of pathological types and clinical epidemiology of 6058 patients with lung cancer[J]. Chinese Journal of Lung Cancer, 2016, 19(3): 129-135.
[3] Novello S, Pimentel FL, Douillard JY, et al. Safety and resource utilization by non-small cell lung cancer histology: results from the randomized phase III study of pemetrexed plus cisplatin versus gemcitabine plus cisplatin in chemonaïve patients with advanced non-small cell lung cancer[J]. J Thorac Oncol, 2010, 5(10): 1602-1608.
[4] Li XQ, Shang BY, Wang DC, et al. Endostar, a modified recombinant human endostatin, exhibits synergistic effects with dexamethasone on angiogenesis and hepatoma growth[J]. Cancer Lett, 2011, 301(2): 212-220.
[5] 王金万, 孙燕, 刘永煜, 等. 重组人血管内皮抑素联合NP方案治疗晚期NSCLC随机、双盲、对照、多中心Ⅲ期临床研究[J]. 中国肺癌杂志, 2005, 8(4): 283-290. WANG Jinwan, SUN Yan, LIU Yongyu, et al. Results of randomized, multicenter, double-blind phase Ⅲ trial of rh-endostatin(YH-16)in treatment of advanced non-small cell lung cancer patients[J]. Chinese Journal of Lung Cancer, 2005, 8(4): 283-290.
[6] Goodman A. Judah Folkman: prediction that broader-spectrum antiangiogenic drugs, lower doses, & continuing doses will improve outcomes[J]. Oncology Times, 2007, 29(2): 38-39.
[7] Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma[J]. N Engl J Med, 1991, 324(1): 1-8.
[8] Folkman J. Tumor angiogenesis: therapeutic implications[J]. N Engl J Med, 1971, 285(21): 1182-1186.
[9] O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesisand tumor growth[J]. Cell, 1997, 88(2): 277-285.
[10] 曲文书, 秦叔逵, 吴穷, 等. 重组人血管内皮抑制素抑制内皮细胞血管生成的实验研究[J]. 临床肿瘤学杂志, 2008, 13(4): 307-312. QU Wenshu, QIN Shukui, WU Qiong, et al. Inhibitory effect of human recombinant endostatin(endostar)on the angiogenesis of HUVECs[J].Chinese Clinical Oncology, 2008, 13(4): 307-312.
[11] Jia H, Kling J. China offers alternative gateway for experimental drugs[J]. Nat Biotechnol, 2006, 24(2): 117-118.
[12] Yao D, Shen H, Huang J, et al. Influence of different drug delivery methods for Endostar combined with a gemcitabine/cisplatin regimen in locally advanced or metastatic lung squamous cell carcinoma: a retrospective observational study[J]. Medicine, 2018, 97(32): e11822. doi:10.1097/MD.0000000000011822.
[13] 吴皎, 杨慧勤, 刘蓉, 等. 恩度微量泵入与腹腔注射联合表阿霉素治疗小鼠乳腺癌的疗效对比观察[J]. 肿瘤防治研究, 2018, 45(7): 463-467. WU Jiao, YANG Huiqin, LIU Rong, et al. Effect of two administration methods of endostar combined with epirubicin on breast cancer in mice[J]. Cancer Research on Prevention and Treatment, 2018, 45(7): 463-467.
[14] 叶振华. 重组人血管内皮抑制素(恩度)的医学观点浅谈[J]. 中国医药前沿, 2009, 4(7): 26-27.
[15] Kisker O, Becker CM, Prox D, et al. Continuous administration of endostatin by intraperitoneally implanted osmotic pump improves the efficacy and potency of therapy in a mouse xenograft tumor model[J]. Cancer Res, 2001, 61(20): 7669-7674.
[16] 原雪, 邹畅, 蒋利平, 等. Endostar体外稳定性研究[J]. 中国药科大学学报, 2009, 40(4): 359-363. YUAN Xue, ZOU Chang, JIANG Liping, et al. In vitro stability of Endostar[J]. Journal of China Pharmaceutical University, 2009, 40(4): 359-363.
[17] Jia Y, Liu M, Huang W, et al. Recombinant human endostatin endostar inhibits tumor growth and metastasis in a mouse xenograft model of colon cancer[J]. Pathol Oncol Res, 2012, 18(2): 315-323.
[18] Arjaans M, Schröder CP, Oosting SF, et al. VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside[J]. Oncotarget, 2016, 7(16): 21247-21258.
[19] Wan YY, Tian GY, Guo HS, et al. Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats[J]. Respir Res, 2013, 14(1): 56. doi:10.1186/1465-9921-14-56.
[20] Yu L, Deng L, Li J, et al. The prognostic value of vascular endothelial growth factor in ovarian cancer: a systematic review and meta-analysis[J]. Gynecol Oncol, 2013, 128(2): 391-396.
[21] Qin RS, Zhang ZH, Zhu NP, et al. Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma[J]. BMC Cancer, 2018, 18(1): 967. doi:10.1186/s12885-018-4738-2.
[22] Yu M, Han Y, Zhuo H, et al. Endostar, a modified endostatin induces vascular normalization to improve chemotherapy efficacy through suppression of src signaling pathway[J]. Cancer Biother Radiopharm, 2018, 33(4): 131-138.
[23] Xu Q, Gu J, Lv Y, et al. Angiogenesis for tumor vascular normalization of Endostar on hepatoma 22 tumor? bearing mice is involved in the immune response[J]. Oncol Lett, 2018, 15(3): 3437-3446.
[24] Li GC, Zhang Z, Ma XJ, et al. Are biomarkers correlated with recurrence patterns in patients with resectable gastric adenocarcinoma[J]. Mol Biol Rep, 2012, 39(1): 399-405.
[25] Zhang J, Liu J, Zhu C, et al. Prognostic role of vascular endothelial growth factor in cervical cancer: a meta-analysis[J]. Oncotarget, 2017, 8(15): 24797-24803.
[26] He Y, Li D, Song G, et al. Lung cancer burden has increased during the last 40 years in Hebei Province, China[J]. Thorac Cancer, 2016, 7(3): 323-332.
[1] DUAN Chu-Hong, LIU Kai, YIN Hai-Yan, ZHAO Shi-Dou, LIU Feng-Tao. Effects of lectin receptors of WGA,RCA and ECL on the development of cleft palate induced by excess retinoid acid in KM mice [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 47-.
[2] HAN Jing, JIA Chunling. Effects of periodontal basic therapy on postoperative pneumonia in patients with lung cancer before thoracic surgery [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 113-118.
[3] GAO Zhongxia, ZHANG Ming, FAN Mingde, TAN Chenyang, WANG Mengdi, WANG Chao, FAN Yuefei, DING Shouluan, WANG Chengwei. Efficacy and prognostic factors of gamma knife in treating 81 cases of brain metastases from lung cancer [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 44-49.
[4] QIN Jing, YANG Fei, CHEN Qian, XIA Handai, LIU Yanguo, WANG Xiuwen. A network meta-analysis of first-line treatment options for patients with advanced driver-gene wild-type and PD-L1 negative non-squamous non-small cell lung cancer [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 74-82.
[5] WANG Fuli, SUN Yinping, QIN Jie, RONG Jiansheng. Efficacy of DC-CIK cells combined with EGFR-TKI for 35 elderly patients with advanced EGFR-mutant lung cancer [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 110-117.
[6] ZHANG Xiufang, LI Peizheng, ZHANG Bohan, SUN Congcong, LIU Yiming. Protective effect and mechanism of growth differentiation factor-15 in LPS-induced models of Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 1-7.
[7] CHEN Zhaobo, FANG Min, XUE Haoran, LIU Chunyan. Deubiquitinase USP35 promotes the cells migration and invasion of non-small cell lung cancer [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 30-37.
[8] JIAN Tianzi, CHEN Nuo, LI Lixiang, LI Yanqing, LI Yan. Effects of D-mannose and glucose on ulcerative colitis in mice [J]. Journal of Shandong University (Health Sciences), 2022, 60(3): 24-28.
[9] Jinming YU,Weiwei YAN,Dawei CHEN. New practice of radio-immunotherapy for lung cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 1-8.
[10] SUI Rongcui, HAN Shuhui, ZHANG Xianzhao, FAN Xintai, WANG Na, HOU Lingxiao, XU Anting. Localization and expression of L-type calcium channel in mice primary endolymph sac epithelium [J]. Journal of Shandong University (Health Sciences), 2021, 59(10): 17-22.
[11] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1-6.
[12] ZHANG Yu, TANG Xing, MA Haitao, JIANG Wei. Value of indocyanine green fluorescence in thoracoscopic segmentectomy [J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 38-42.
[13] ZHANG Xiqin, ZHU Shouhui, LIU Ning, WANG Yu, CHEN Jiazhen, HU Xudong. Clinical observation of PEG-rhG-CSF in preventing neutropenia in 80 patients with small cell lung cancer treated with concurrent chemoradiotherapy [J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 43-46.
[14] LIU Xiaojing, XIA Xiyan, XIAO Ke, CHEN Wendan, ZHUANG Xuewei. Expression and clinical significance of exosomal long non-coding RNA OGFRP1 in 84 cases of non-small cell lung cancer [J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 71-75.
[15] WEI Ping, DU Lutao, WANG Qing, ZHAN Yao, XIE Yujiao, ZHANG Shujun, DUAN Weili, WANG Chuanxin. Diagnostic value of serum exosomal miR-20b-5p for non-small cell lung cancer [J]. Journal of Shandong University (Health Sciences), 2019, 57(4): 91-96.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd