An Evaluation of HER2-Positive Ovarian Carcinoma Xenografts: From a Novel Therapy to a Noninvasive Monitoring Method

被引：3
作者：
Hong, Zhihui [1 ]
Mao, Xinping [2 ]
You, Jiaxi [1 ]
Liu, Zengli [1 ]
Shi, Yizhen [1 ]
机构：
[1] Soochow Univ, Affiliated Hosp 2, Dept Nucl Med, 1055 Sanxiang Rd, Suzhou 215004, Peoples R China
[2] GanSu Univ Chinese Med, Div Med Imageol, Lanzhou, Gansu, Peoples R China
来源：
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS | 2018年 / 33卷 / 09期
关键词：
cisplatin; HER2; ovarian carcinoma; single-photon emission computed tomography (SPECT); siRNA; BREAST-CANCER; TRASTUZUMAB; RNA; EXPRESSION; ADENOVIRUS; ERBB2;
D O I：
10.1089/cbr.2018.2516
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Purpose: Overexpression of the HER2/neu (HER2) is linked to an adverse outcome in ovarian cancer. Short-interfering RNA (siRNA) is a HER2 inhibitor, which in combination with chemotherapy improves survival rate. The aim of this study was to evaluate the efficacy of adenovirus mediated HER2-siRNA in combination with cisplatin (Ad-HER2-siRNA+DDP) on treating HER2-positive ovarian cancer xenografts and explore the effectiveness of I-131-Herceptin immunoSPECT imaging for monitoring the tumor's progression. Methods: Mice with ovarian cancer xenografts were treated with different therapy regimens and imaged at 1, 4, 8, 12, 24, 48, 72, and 96 h postinjection with I-131-Herceptin. Concurrently, the tumor/background (T/B) ratios were calculated. In addition, HER2 protein expression levels were determined by immunohistochemistry (IHC). Results: The in vivo therapy experiments revealed that tumor weight and volume of Ad-HER2-siRNA+DDP group was the least of all. The IHC results further confirmed that HER2 protein level was significantly downregulated in this group. The results of SPECT imaging showed that the T/B ratios at each time point in Ad-HER2-siRNA +DDP group was the lowest (p < 0.05). Conclusions: The data demonstrate that the growth of xenografts of human ovarian cancer with high expression of HER2 could be inhibited effectively by Ad-HER2-siRNA+DDP. I-131-Herceptin had potential use for noninvasive imaging of HER2 expression.
引用
收藏
页码：411 / 419
页数：9
相关论文
共 27 条
[1]   RNA-dependent RNA polymerases, viruses, and RNA silencing [J].
Ahlquist, P .
SCIENCE, 2002, 296 (5571) :1270-1273
[2]   Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin [J].
Austin, CD ;
De Mazière, AM ;
Pisacane, PI ;
van Dijk, SM ;
Eigenbrot, C ;
Sliwkowski, MX ;
Klumperman, J ;
Scheller, RH .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (12) :5268-5282
[3]  
Bang YJ, 2010, LANCET, V376, P1302
[4]   Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer [J].
Baselga, Jose ;
Cortes, Javier ;
Kim, Sung-Bae ;
Im, Seock-Ah ;
Hegg, Roberto ;
Im, Young-Hyuck ;
Roman, Laslo ;
Pedrini, Jose Luiz ;
Pienkowski, Tadeusz ;
Knott, Adam ;
Clark, Emma ;
Benyunes, Mark C. ;
Ross, Graham ;
Swain, Sandra M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (02) :109-119
[5]   Current research in nuclear medicine and molecular imaging: highlights of the 23rd Annual EANM Congress [J].
Carrio, Ignasi .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2011, 38 (02) :378-399
[6]   Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging [J].
Dijkers, Eli C. F. ;
Kosterink, Jos G. W. ;
Rademaker, Anna P. ;
Perk, Lars R. ;
van Dongen, Guus A. M. S. ;
Bart, Joost ;
de Jong, Johan R. ;
de Vries, Elisabeth G. E. ;
Lub-de Hooge, Marjolijn N. .
JOURNAL OF NUCLEAR MEDICINE, 2009, 50 (06) :974-981
[7]   Differential immune responses mediated by adenovirus- and lentivirus-transduced DCs in a HER-2/neu overexpressing tumor model [J].
Felizardo, T. C. ;
Wang, J. C. M. ;
McGray, R. A. J. ;
Evelegh, C. ;
Spaner, D. E. ;
Fowler, D. H. ;
Bramson, J. L. ;
Medin, J. A. .
GENE THERAPY, 2011, 18 (10) :986-995
[8]   Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer [J].
Jiang, Dawei ;
Im, Hyung-Jun ;
Sun, Haiyan ;
Valdovinos, Hector F. ;
England, Christopher G. ;
Ehlerding, Emily B. ;
Nickles, Robert J. ;
Lee, Dong Soo ;
Cho, Steve Y. ;
Huang, Peng ;
Cai, Weibo .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2017, 44 (08) :1296-1305
[9]   Analysis of Her2/neu membrane protein clusters in different types of breast cancer cells using localization microscopy [J].
Kaufmann, R. ;
Mueller, P. ;
Hildenbrand, G. ;
Hausmann, M. ;
Cremer, C. .
JOURNAL OF MICROSCOPY, 2011, 242 (01) :46-54
[10]   Cisplatin resistance: Preclinical findings and clinical implications [J].
Koeberle, Beate ;
Tomicic, Maja T. ;
Usanova, Svetlana ;
Kaina, Bernd .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2010, 1806 (02) :172-182
123