Malekian Saba, Rahmati Marveh, Sari Soyar, Kazemimanesh Monireh, Kheirbakhsh Raheleh, Muhammadnejad Ahad, Amanpour Saeid
Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Molecular and Cellular Sciences, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Adv Pharm Bull. 2020 Jun;10(2):323-328. doi: 10.34172/apb.2020.039. Epub 2020 Feb 18.
Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model. Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (<100 mm), intermediate stage (100-300 mm), advanced stage (300-500 mm), and end stage (>500 mm), they were removed by surgery. Then, the expression levels of Hif1α, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16. TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically. The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC.
三阴性乳腺癌（TNBC）的特点是血管丰富且易反复转移。尽管多项研究表明血管生成在浸润性乳腺癌中起重要作用，但仍需要开发一种能够准确显示血管生成因子确切起始情况的合适TNBC模型。本研究的目的是确定作为TNBC小鼠模型的4T1肿瘤在不同临床阶段血管生成因子的表达水平。给20只小鼠注射4T1细胞系，选取4只小鼠作为健康对照。肿瘤诱导后，将小鼠随机分为四组，每组四只。一旦肿瘤体积达到早期（<100立方毫米）、中期（100 - 300立方毫米）、晚期（300 - 500立方毫米）和终末期（>500立方毫米），就通过手术将它们移除。然后，分别通过qPCR和免疫组织化学（IHC）评估Hif1α、VEGFR1和VEGFR2基因的表达水平，以及VEGF、bFGF和CD31的肿瘤标志物。使用SPSS 16版进行统计分析。确认了TNBC肿瘤，并在肺部发现了多灶性转移。血管生成因子的mRNA和蛋白质表达水平在早期升高，并且随着肿瘤生长，其表达水平显著增强。4T1同基因小鼠肿瘤可作为进一步研究血管生成和治疗方法的合适TNBC模型。此外，血管生成因子在晚期之前就被诱导，在TNBC的一线治疗中必须考虑抗血管生成治疗。
