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与K-ras基因错配突变的反义寡核苷酸对仓鼠胰腺癌细胞系侵袭的抑制作用

Suppression of invasion of a hamster pancreatic cancer cell line by antisense oligonucleotides mutation-matched to K-ras gene.

作者信息

Morioka Cintia Yoko, Machado Marcel Cerqueira Cesar, Saito Seiji, Nakada Yuji, Matheus André Siqueira, Jukemura José, Bacchella Telesforo, Takahara Terumi, Watanabe Akiharu

机构信息

Department of Surgery, University of São Paulo, São Paulo, Brazil.

出版信息

In Vivo. 2005 May-Jun;19(3):535-8.

PMID:15875772
Abstract

The anti-invasive activity of antisense oligonucleotides (ASO) specific to the K-ras gene in hamster pancreatic cancer was investigated. HaP-T1, a cell culture derived from BHP-induced hamster pancreatic cancer, was used. After liposome-mediated transfection with mutation-matched and mutation-mismatched ASO in different concentrations, cell proliferation was studied by MTT and MTT-agarose methods. In vitro chemoinvasion assay with the reconstitution of a matrix of a basement membrane onto a filter in a Boyden chamber was performed. Mutation-matched ASO inhibited the tumor growth and invasiveness of HaP-T1 in a dose-dependent manner, while mutation-mismatched ASO were not effective in inhibiting invasion. The present study suggests that antisense oligonucleotides mutation-matched to the K-ras gene may be a new anticancer strategy for pancreatic cancer since they inhibited not only tumor growth but also invasiveness in vitro.

摘要

研究了针对K-ras基因的反义寡核苷酸(ASO)对仓鼠胰腺癌的抗侵袭活性。使用了HaP-T1细胞,它是由BHP诱导的仓鼠胰腺癌衍生而来的细胞培养物。在不同浓度下用突变匹配和突变错配的ASO进行脂质体介导的转染后,通过MTT和MTT-琼脂糖方法研究细胞增殖。在Boyden小室中,在滤膜上重建基底膜基质进行体外化学侵袭试验。突变匹配的ASO以剂量依赖的方式抑制HaP-T1的肿瘤生长和侵袭性,而突变错配的ASO在抑制侵袭方面无效。本研究表明,与K-ras基因匹配的反义寡核苷酸可能是一种新的胰腺癌抗癌策略,因为它们不仅在体外抑制肿瘤生长,还抑制侵袭性。

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