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SU11274抑制胰腺癌细胞的增殖和运动能力。

SU11274 suppresses proliferation and motility of pancreatic cancer cells.

作者信息

Tomizawa Minoru, Shinozaki Fuminobu, Motoyoshi Yasufumi, Sugiyama Takao, Yamamoto Shigenori, Ishige Naoki

机构信息

Department of Gastroenterology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.

Department of Radiology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.

出版信息

Oncol Lett. 2015 Sep;10(3):1468-1472. doi: 10.3892/ol.2015.3452. Epub 2015 Jul 2.

Abstract

Mesenchymal-epithelial transition factor (c-Met) is associated with the proliferation and motility of cancer cells. c-Met expression has been detected in surgical pancreatic cancer specimens, and its overexpression is associated with a poor prognosis. SU11274 is a specific inhibitor of c-Met. In the present study, the cell proliferation and motility of pancreatic cancer cells treated with SU11274 was investigated. The PANC-1, MIA-Paca2, NOR-P1, PK-45H, PK-1 and PK-59 pancreatic cancer cell lines were used. The expression of c-Met and cyclin D1 was analyzed by quantitative polymerase chain reaction. In addition, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt assay was performed to assess cell proliferation, and a scratch assay was performed to assess cell motility. c-Met expression was higher in PANC-1, PK-45H, PK-1 and PK-59 cell lines compared with that in normal pancreatic tissue. Following treatment with 30 µM SU11274, the proliferation of MIA-Paca2 and PK-45H cells was suppressed to 19.8±10.7% (P<0.05) and 45.8±14.8% (P<0.05) of the control level, respectively. Furthermore, cyclin D1 expression was downregulated to 43.7±17.9% (P<0.05) and 53.2±18.6% (P<0.05) of the control level in the MIA-Paca2 and PK-45H cell lines, respectively, following treatment with 30 µM SU11274. In addition, cell motility was reduced to 1.0±0.3% in MIA-Paca2 (P<0.05) and 14.7±3.5% in PK-45H (P<0.05) following treatment with 30 µM SU11274, compared with the motility of untreated cells. These results indicated that SU11274 suppresses the proliferation of pancreatic cancer cells via the downregulation of cyclin D1. The present study also demonstrated that cell motility was suppressed by treatment with SU11274.

摘要

间充质上皮转化因子(c-Met)与癌细胞的增殖和运动有关。在胰腺癌手术标本中已检测到c-Met表达,其过表达与预后不良相关。SU11274是c-Met的特异性抑制剂。在本研究中,对用SU11274处理的胰腺癌细胞的细胞增殖和运动进行了研究。使用了PANC-1、MIA-Paca2、NOR-P1、PK-45H、PK-1和PK-59胰腺癌细胞系。通过定量聚合酶链反应分析c-Met和细胞周期蛋白D1的表达。此外,进行了3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑内盐测定以评估细胞增殖,并进行划痕试验以评估细胞运动。与正常胰腺组织相比,PANC-1、PK-45H、PK-1和PK-59细胞系中的c-Met表达更高。用30μM SU11274处理后,MIA-Paca2和PK-45H细胞的增殖分别被抑制至对照水平的19.8±10.7%(P<0.05)和45.8±14.8%(P<0.05)。此外,用30μM SU11274处理后,MIA-Paca2和PK-45H细胞系中细胞周期蛋白D1的表达分别下调至对照水平的43.7±17.9%(P<0.05)和53.2±18.6%(P<0.05)。此外,与未处理细胞的运动相比,用30μM SU11274处理后,MIA-Paca2细胞的运动降低至1.0±0.3%(P<0.05),PK-45H细胞的运动降低至14.7±3.5%(P<0.05)。这些结果表明,SU11274通过下调细胞周期蛋白D1来抑制胰腺癌细胞的增殖。本研究还表明,用SU11274处理可抑制细胞运动。

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c-Met inhibitors.c-Met 抑制剂。
Infect Agent Cancer. 2013 Apr 8;8(1):13. doi: 10.1186/1750-9378-8-13.
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Microenvironment elements involved in the development of pancreatic cancer tumor.参与胰腺癌肿瘤发展的微环境元素。
Gastroenterol Res Pract. 2012;2012:585674. doi: 10.1155/2012/585674. Epub 2012 Dec 13.

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