Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gene therapy system

	Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gene therapy system
	Hayashi, K ; Hayashi, T ; Sun, HD; Takeda, Y
	2002-02-01
发表期刊	HUMAN GENE THERAPY
卷号	13 期号:3 页码:415-423
摘要	We have previously reported that ponicidin (PND), isolated from Rabdosia ternifolia, potentiates the cell-killing activity of antiherpes prodrugs acyclovir (ACV) and ganciclovir (GCV) in human cancer cells expressing herpes simplex virus thymidine kinase (HSV-TK). To extend these in vitro results to in vivo situations, HSV-TK-expressing HeLa cells were injected into nude mice. The in vivo growth of TK+ HeLa cells was significantly inhibited by coadministration of PND and ACV, or of PND and GCV, compared with single use of ACV or GCV in spite of lower doses of 1 or 0.25 mg/mouse, respectively. These results indicate that there is a good correlation between this in vivo efficacy and previously reported in vitro efficacy. Because of the insufficiency of incorporation of genes into tumors, bystander cell killing has attracted special interest. In the present study, we determined the ability of PND to potentiate the bystander effects of ACV and GCV in both in vitro and in vivo systems. In vitro combined use of PND with ACV or GCV rendered tumor cells more sensitive to the prodrugs, demonstrating a 1.8- to 97-fold or 2.8- to 26-fold reduction in IC50 compared with ACV or GCV only, respectively, in 1 to 20% of HSV-TK+ cells. In the in vivo experiments using nude mice injected with 3 or 10% HSV-TK+ cells, tumor volume was lower in mice treated with a combination of PND and ACV/GCV than in those treated with ACV or GCV only. No toxicity of PND was seen in mice even at a dose 10-fold higher than that used in the in vivo experiments. These novel strategies could provide benefit to ablative cancer gene therapy by making it feasible to use toxic GCV at lower doses and relatively nontoxic ACV.
收录类别	SCI
语种	英语
WOS记录号	WOS:000174120900007
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/23978
专题	植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.Toyama Med & Pharmaceut Univ, Dept Virol, Toyama 9300194, Japan 2.Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama 9300194, Japan 3.Acad Sinica, Kunming Inst Bot, Kunming 650107, Yunnan, Peoples R China 4.Univ Tokushima, Fac Integrated Arts & Sci, Tokushima 7700814, Japan
推荐引用方式 GB/T 7714	Hayashi, K,Hayashi, T,Sun, HD,et al. Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gene therapy system[J]. HUMAN GENE THERAPY,2002,13(3):415-423.
APA	Hayashi, K,Hayashi, T,Sun, HD,&Takeda, Y.(2002).Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gene therapy system.HUMAN GENE THERAPY,13(3),415-423.
MLA	Hayashi, K,et al."Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gene therapy system".HUMAN GENE THERAPY 13.3(2002):415-423.

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