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使用胰腺导管腺癌细胞系构建的新型原位腹膜播散小鼠模型的建立及生物学分析

Development and Biological Analysis of a Novel Orthotopic Peritoneal Dissemination Mouse Model Generated Using a Pancreatic Ductal Adenocarcinoma Cell Line.

作者信息

Yanagihara Kazuyoshi, Kubo Takanori, Mihara Keichiro, Kuwata Takeshi, Ochiai Atsushi, Seyama Toshio, Yokozaki Hiroshi

机构信息

Department of Life Sciences, Yasuda Women's University Faculty of Pharmacy.

Department of Hematology/Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima.

出版信息

Pancreas. 2019 Mar;48(3):315-322. doi: 10.1097/MPA.0000000000001253.

Abstract

OBJECTIVES

Peritoneal dissemination (PD) is an important cause of morbidity and mortality among patients with pancreatic ductal adenocarcinoma (PDAC). We sought to develop and characterized a novel PD mouse model by using a previously established PDAC cell line TCC-Pan2.

METHODS

TCC-Pan2 cell line was characterized for growth rate, tumor markers, histology, and somatic mutations. TCC-Pan2 cells were implanted orthotopically to produce PD. TCC-Pan2 cells from these metastatic foci were expanded in vitro and then implanted orthotopically in mice. This PD model was used for comparing the antitumor effect of paclitaxel and NK105.

RESULTS

Orthotopically implanted TCC-Pan2 cells caused tumor formation and PD with high frequency in mice. A potent metastatic subline-Pan2M-was obtained. NK105 exerted a stronger antitumor effect than paclitaxel against Pan2M cells harboring a luciferase gene (Pan2MmLuc). Notably, the survival rate on day 80 in the Pan2MmLuc mouse model was 100% for the NK105 group and 0% for the paclitaxel group.

CONCLUSION

TCC-Pan2 cell line and Pan2MmLuc PD model can serve as useful tools for monitoring the responses to antineoplastic agents and for studying PDAC biology.

摘要

目的

腹膜播散(PD)是胰腺导管腺癌(PDAC)患者发病和死亡的重要原因。我们试图通过使用先前建立的PDAC细胞系TCC-Pan2来开发并表征一种新型的PD小鼠模型。

方法

对TCC-Pan2细胞系进行生长速率、肿瘤标志物、组织学和体细胞突变方面的表征。将TCC-Pan2细胞原位植入以产生PD。从这些转移灶中获取的TCC-Pan2细胞在体外扩增,然后原位植入小鼠体内。该PD模型用于比较紫杉醇和NK105的抗肿瘤效果。

结果

原位植入的TCC-Pan2细胞在小鼠中高频诱导肿瘤形成和PD。获得了一个高转移性亚系——Pan2M。NK105对携带荧光素酶基因的Pan2M细胞(Pan2MmLuc)的抗肿瘤作用比紫杉醇更强。值得注意的是,在Pan2MmLuc小鼠模型中,第80天时NK105组的生存率为100%,紫杉醇组为0%。

结论

TCC-Pan2细胞系和Pan2MmLuc PD模型可作为监测抗肿瘤药物反应和研究PDAC生物学的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1a5/6426353/30c809cf775d/mpa-48-315-g001.jpg

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