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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05557084/
• 关键词: Human salivary cancer cells; Cellular differentiation-inducing agents; Screening system; Salivary adenoid squamous carcinoma-forming cells; DNA hypomethylation; Apoptosis; Anti-tumor agents; 口腔小唾液腺由来腺様扁平上皮癌細胞; 造腫瘍性ヒト腺房細胞癌細胞; 分化誘導剤

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.从人涎腺癌细胞株HSG中分离到神经元样细胞(HSG-AZAll)，细胞内含有丰富的神经丝束和内质网以及微管蛋白的α-链和β-链。发现HSG-AZAll细胞可形成突起，并表达突触素和神经元特异性烯醇化酶对二丁酰环AMP的反应，这表明HSG-AZAll细胞可能有助于寻找通过cAMP信号转导作用的细胞分化诱导剂。2.我们发现5-氟代脱氧尿苷单磷酸处理HSG细胞可诱导其向肌上皮细胞分化，并诱导细胞凋亡。3.用5-氮胞苷和3，4-dihydro-6-[3，4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-喹诺酮(维司力农)诱导HSG-AZA_3细胞向软骨细胞分化，细胞表型为腺泡细胞。此外，它还具有b-…。进一步发现，用22-氧杂-1α，25-二羟基维生素D_3处理HSG-AZA3细胞可诱导其向成骨细胞分化。4.我们发现用DNA拓扑异构酶II的抑制剂依托泊苷处理HSG细胞，可以诱导出具有平滑肌细胞表型的细胞，如α-平滑肌肌动蛋白和肌丝的表达，并诱导细胞凋亡。5.用5-氟尿嘧啶或维司力农处理口腔内人小唾液腺来源的腺样鳞癌形成细胞(TYS)，发现TYS细胞具有诱导凋亡和向腺泡细胞分化的作用。6.用22-OXA-1α，25(OH)_2D_3处理HSG-AZA3裸鼠移植瘤，可明显抑制肿瘤的生长，表现出明显的骨形成和骨重建。7.用维司力农治疗TYS裸鼠肿瘤时，肿瘤生长受到明显抑制，并向角质形成细胞和腺泡细胞分化。较少

项目成果

Hideo Yoshida: "Emergence of a smooth muscle cell phenotype and apoptosis by treatment with etoposide,an inhibitor of DNA topoisomerase II,in a neoplastic human salivary intercalated duct cell line" Cancer Journal. 6. 220-228 (1993)

Hideo Yoshida：“用依托泊苷（一种 DNA 拓扑异构酶 II 抑制剂）治疗肿瘤性人唾液闰管细胞系时出现平滑肌细胞表型和凋亡”《癌症杂志》。

東雅之: "SV40不死化正常ヒト唾液腺細胞における野生型P53の発現" 日本口腔科学会雑誌. 43. 580-589 (1994)

Masayuki Azuma：“野生型 P53 在 SV40 永生化正常人唾液腺细胞中的表达”日本口腔医学会杂志 43. 580-589 (1994)。

東 雅之: "SV40 不死化正常ヒト唾液腺細胞における野生型P53の発現" 日本口腔科学会雑誌. 43. 580-589 (1994)

Masayuki Higashi：“野生型 P53 在 SV40 永生化正常人唾液腺细胞中的表达”日本口腔医学会杂志 43. 580-589 (1994)。

佐藤光信: "唾液腺腫瘍の分化誘導療法" 癌と化学療法. 20. 1028-1036 (1993)

Mitsunobu Sato：“唾液腺肿瘤的分化诱导疗法”《癌症与化疗》20。1028-1036（1993）。

Mitsunobu Sato: "Induction of differentiation and apoptosis, and Le^Y antigen expression by treatment with 3,4-dihydro-6-〔4-(3,4-dimethoxybenzoy1)-1-piperaziny1〕-2(1H)-quinolinone(vesnarinone)in a human salivary cancer cell line" Acta Histochem.Cytochem.

Mitsunobu Sato：“用 3,4-二氢-6-[4-(3,4-二甲氧基苯甲酰基 1)-1-哌嗪基 1]-2(1H)-喹啉酮处理诱导分化和凋亡，以及 Le^Y 抗原表达( vesnarinone）在人唾液癌细胞系中的作用“Acta Histochem.Cytochem。