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[干扰素增强抗肿瘤药物的细胞毒性作用]

[Enhanced cytotoxicity of antineoplastics by interferon].

作者信息

Yoneda K, Yamamoto T, Osaki T

机构信息

Department of Dentistry and Oral Surgery, Kochi Medical School.

出版信息

Nihon Gan Chiryo Gakkai Shi. 1990 Jan 20;25(1):77-84.

PMID:2109027
Abstract

Cytotoxicities of bleomycin (BLM), vincristine (VCR) and adriamycin (ADM), and influence of interferon (IFN) on their effects were examined on three tumor cell lines of HeLa, HSG (established from human submandibular gland) and Muko cells (derived from mucoepidermoid tumor of the upper jaw). Both human natural interferon beta (IFN beta) and recombinant interferon gamma (IFN gamma) exhibited anticellular activities. Antiproliferative action, and DNA and protein synthesis inhibition of each anticancer drug on tumor cells were enhanced by a few hrs' IFN (100 IU/ml) pretreatment. In these, DNA synthesis inhibition was more exaggerated. Cooperative IFN effects were additive in general while showing slight synergistic inhibitory action on DNA synthesis. Enhanced in vitro cytotoxic effects of the anticancer drugs by IFNs were similarly identified in tumor cell-inoculated nu/nu mice which were treated twice a week with locally injected IFN gamma and antineoplastics. Proliferation of inoculated tumor cells was significantly suppressed by IFN gamma, and a cooperative effect of the IFN and drugs was obtained. Concentrations of intracellular anticancer drugs were heightened by IFN pretreatment. From these results, IFN seemed to contribute to the enhanced anticellular effects of BLM, VCR and ADM by affecting cellular uptake of the drugs.

摘要

研究了博来霉素(BLM)、长春新碱(VCR)和阿霉素(ADM)对三种肿瘤细胞系(HeLa、HSG(源自人下颌下腺)和Muko细胞(源自上颌黏液表皮样肿瘤))的细胞毒性,以及干扰素(IFN)对其作用的影响。人天然干扰素β(IFNβ)和重组干扰素γ(IFNγ)均表现出抗细胞活性。通过数小时的IFN(100 IU/ml)预处理,每种抗癌药物对肿瘤细胞的抗增殖作用以及DNA和蛋白质合成抑制作用均增强。其中,DNA合成抑制更为明显。IFN的协同作用一般为相加作用,同时对DNA合成表现出轻微的协同抑制作用。在每周两次局部注射IFNγ和抗肿瘤药治疗的接种肿瘤细胞的裸鼠中,同样发现IFN增强了抗癌药物的体外细胞毒性作用。IFNγ显著抑制了接种肿瘤细胞的增殖,并获得了IFN与药物的协同作用。IFN预处理提高了细胞内抗癌药物的浓度。从这些结果来看,IFN似乎通过影响药物的细胞摄取,促进了BLM、VCR和ADM的增强抗细胞作用。

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