米德金
感应(电子)
转染
癌症研究
血管生成
分子生物学
癌变
反义治疗
体外
溴脱氧尿苷
生物
化学
生长因子
细胞培养
癌症
医学
细胞生长
内科学
寡核苷酸
受体
生物化学
基因
锁核酸
物理化学
遗传学
作者
Yoshiyuki Takei,Kenji Kadomatsu,Seiichi Matsuo,Hiroshi Itoh,Kumiko Nakazawa,Shunichiro Kubota,Takashi Muramatsu
出处
期刊:PubMed
日期:2001-12-01
卷期号:61 (23): 8486-91
被引量:46
摘要
Midkine (MK), a heparin-binding growth factor, is overexpressed in a wide range of human carcinomas and is believed to contribute to tumorigenesis and tumor progression. To develop an antitumor reagent, we designed a phosphorothioate antisense oligodeoxynucleotide molecule based on the secondary structure of MK mRNA. The antisense MK at the dosage of 5 microM suppressed MK production by CMT-93 mouse rectal carcinoma cells after cationic liposome-mediated transfection, to 13% of that in control cultures. The growth of CMT-93 cells and their colony formation in soft agar were inhibited by the addition of the antisense MK, whereas the control reagent, the sense MK, showed no effects. On s.c. injection into nude mice, CMT-93 cells transfected with the antisense MK formed tumors much smaller than those by control cells. Finally, untreated CMT-93 cells were inoculated to nude mice, and 7 days later the antisense MK (50 microM) with atelocollagen was directly injected into the preformed tumor region to evaluate the curative effect; the injection was repeated at the interval of 2 weeks. During the period of 10-41 days after initiation of therapy, the rate of increase of tumor volume treated with the antisense MK was found to be about 4.2-fold lower than that seen after treatment with the sense MK. On this occasion, proliferation of tumor cells as estimated by 5-bromodeoxyuridine incorporation was strongly inhibited, whereas angiogenesis was less affected. These findings strongly suggested the usefulness of MK antisense oligodeoxynucleotide as a new reagent for cancer therapy.
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