Development of screening system for searching cellular differentiation-inducing agents by utlizing human salivary cancer cells

开发利用人唾液癌细胞寻找细胞分化诱导剂的筛选系统

基本信息

批准号：
05557084
负责人：
SATO Mitsunobu
金额：
$ 7.04万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

1.Neuron-like cells (HSG-AZAll) with ample neurofilament bundles and endoplasmic reticulum as well as alpha-and beta-chain of tubulin were isolated from human salivary cancer cell line HSG treated with 5-azactidine. This HSG-AZAll cells were found to from neurites and express synaptophysin and neuron-specific enolase in response to dibutyryl cyclic AMP.This indicated that HSG-AZAll cells might be useful for searching cellular differentiation-inducing agents which work via cAMP signal transduction. 2.We have found that the treatment of HSG cells with 5-fluorodeoxyuridine monophosphate results in the differentiation into myoepithelial cells and induciton of apoptosis. 3.We have found that the cultivation of HSG-AZA3 cells with an acinar cell phenotype, which were induced by treatment of HSG cells with 5-azacytidine, in the presence of 3,4-dihydro-6-[3,4-dimethoxybenzoyl)-1-piperazinyl]-2 (1H) -quinolnone (vesnarinone) results in the differentiation into chondrocytes.In addition, it has b … More een found that the treatment of HSG-AZA3 cells with 22-oxa-1alpha, 25-dihydroxyvitamin D_3 causes the differentiation into osteoblasts. 4.We have found that the treatment of HSG cells with etoposide, an inhibitor of DNA topoisomerase II,results in the induction of cells with a smooth muscle cell phenotype, such as expression of alpha-smooth muscle actin and myofilaments, as well as in the induction of apoptosis. 5.When adenoid squamous carcinoma-forming cells (TYS) , derived from human minor salivary gland present in the oral cavity, was treated with 5-fluorouracil or vesnarinone, it has been found that the induction of apoptosis and differentiation into acinar cells occurs in the treated cells. 6.The treatment with 22-oxa-1alpha, 25 (OH) _2D_3 of HSG-AZA3 cells grown as xenografts in nude mice resulted in the marked growth inhibition of tumors, in which bone formation and bone remodeling were detected. 7.When TYS nude mouse tumors were treated with vesnarinone, significant suppression of tumor growth as well as differentiation into both keratinocytes and acinar cells were detected in the treated tumors. Less

1。具有充足的神经丝束和内质网状细胞（HSG-ASGALL），以及从人类唾液癌细胞系HSG的α链，并从5-氮杂氨酸中治疗。突触素和神经元特异性酶响应对脱晶环状AMP的反应。这表明通过cAMP信号转导处理HSG细胞的细胞差异剂可能是使用5-氟二磷酸酯单磷酸盐的细胞差异。 3。我们发现，在存在3,4-二氢-6- [3,4-二甲氧基苯甲酰氮的存在下，用腺泡细胞表型-Azytidine培养HSG-AZA3细胞-2-dimethoxybenzoyl）-2 -2-Piperaziny（1H）-Quinolnone ation-quinolnone ation ation此外，它还具有B…更多的EEN发现HSG-AZA3细胞用22-oxa-1alpha E的治疗发现了用依ETOPOSIS（DNA拓扑异构酶II的过度蛋白酶）处理HSG细胞，从而导致与细胞指示的DNA拓扑异构酶II平滑的肌肉细胞表型，例如α-光滑肌肉肌动蛋白的表达和肌细胞肌细胞的凋亡。 OXA-1Alpha，25（OH）_2D_3的裸鼠中的HSG-AZA3 cenograpts导致明显的肿瘤抑制作用。角质形成细胞和腺泡细胞都在较少的肿瘤中检测到。