Study of Differentiation Therapy for Salivary Gland Cancer

唾液腺癌的分化治疗研究

• 批准号: 03454467
• 负责人: SATO Mitsunobu
• 金额: $ 4.48万
• 依托单位: THE UNIVERSITY OF TOKUSHIMA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454467/
• 关键词: Human salivary gland cancer cells; Hexamethylene bisacetamide; 8-chloroadenosine 3' : 5'-cyclic monophosphate; Differentiation therapy; Protein kinase C; Protein kinase A; dibutyryl cAMP; DNA hypomethylation; Hexamethylene bisacetamide; 8-chloroa

1. Treatment by hexamethylene bisacetamide (HMBA) or 8-chloroadenosine 3' : 5' -cyclic monophosphate (8-Cl-cAMP) of human salivary gland cancer cells (HSG and HSY), which were grown in vitro and as xenograft in nude mouse, resulted in marked growth inhibition. 2. We have already found that be treatment of HSG cells with 5-azacytidine results in the differentiation into myoepithelial cells (HSG-AZA1) and acinar cells (HSG-AZA3). In the present study, we have found that differentiation into the neuron-like cells of HSG-AZA1 cells occurs in growth medium containing 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7), an inhibitor of protein kinase C.When the isoenzymic patterns of protein kinase C in HSG-AZA1 cells were analyzed, expression of all the 3 types of isoenzyme was found in the cells ; however, decreased expression of type II protein kinase C was observed in the HSG-AZA1 cells treated with H-7, as compared with untreated cells. In addition, we have found that treatment of HSG-AZA1 cells with dibutyryl cAMP results in the differentiation into neuron-like cells. 3. Treatment of HSG cells with HuIFN-a significantly decreased the number of EGF receptors/cell. 4. Treatment of HSG or HSG-AZA1 cells with HMBA resulted in the differentiation into glial cells, which was accompanied by the appearance of DNA hypomethylation and decreased expression of type II protein kinase C in the treated cells. 5. It has been suggested that selective binding of 8-Cl-cAMP to cAMP-dependent protein kinase A receptor present in HSG or HSY cells caused marked growth inhibition. 6. The cultivation of HSG cells in the presence of etoposide, an inhibitor of DNA topoisomerse II, resulted in the emergence of cells with a smooth muscle cell phenotype, such as expression of a-smooth muscle actin and myofilaments, which was accompanied by decreased expression of ras oncogene product as compared with the untreated cells. 7. We have prepared the metastasizing HSG cells (mHSG) by treating non-met

1.六亚甲基双乙酰胺(HMBA)或8-氯腺苷3‘：5’-环磷酸腺苷(8-Cl-cAMP)对体外培养的人涎腺癌细胞(HSG和HSY)及裸鼠移植瘤均有明显的生长抑制作用。2.我们已经发现5-氮胞苷作用于HSG细胞可诱导其分化为肌上皮细胞(HSG-AZA1)和腺泡细胞(HSG-AZA3)。在本研究中，我们发现HSG-AZA1细胞分化为神经元样细胞是在含有蛋白激酶C抑制剂1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7)，的培养液中发生的。当分析HSG-AZA1细胞中蛋白激酶C的同工酶时，发现这三种类型的同工酶在细胞中都有表达，但H-7处理的HSG-AZA1细胞中II型蛋白激酶C的表达比未处理的细胞减少。此外，我们还发现用二丁酰cAMP处理HSG-AZA1细胞可以诱导其分化为神经元样细胞。3.人干扰素-α作用于HSG细胞后，细胞内EGF受体数量明显减少。4.HMBA作用于HSG或HSG-AZA1细胞后，细胞分化为神经胶质细胞，并伴有DNA低甲基化和II型蛋白激酶C表达下降。5.8-氯-cAMP与HSG或HSY细胞中cAMP依赖的蛋白激酶A受体的选择性结合可显著抑制细胞的生长。6.在DNA拓扑异构酶II的抑制剂依托泊苷的作用下，HSG细胞出现了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，并伴随着ras癌基因产物表达的降低。7.用非金属硫代巴比妥酸(Non-Met)处理制备了转移HSG细胞

项目成果

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: "5-azacytidine induction of neuron-like cells from a neoplastic human salivary intercalated duct cell line and effect of dibutyryl cyclic adenosine 3' : 5'-monophosphate on proliferation and phenotype of the induced cells" Cancer Journal.

Mitsunobu Sato：“5-氮杂胞苷诱导来自肿瘤性人唾液闰管细胞系的神经元样细胞，以及二丁酰环腺苷 3 : 5-单磷酸对诱导细胞增殖和表型的影响”《癌症杂志》。

Masayuki Azuma: "Role of plasminogen activators,metalloproteinases and tissue inhibitor of metalloproteinse-1 in the metastatic process of human salivary gland adenocarcinoma cells." International Journal of Cancer. 54. 669-676 (1993)

Masayuki Azuma：“纤溶酶原激活剂、金属蛋白酶和金属蛋白酶-1 组织抑制剂在人唾液腺腺癌细胞转移过程中的作用。”

Hidio Yoshida: "Induction of cells with phenotypic features on neuronal cells by treatment with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) in an human salivary myoepithelial cell line in culture and isoenzymic patterns of protein kinase C in the

Hidio Yoshida：“在培养的人唾液肌上皮细胞系中用 1-(5-异喹啉基磺酰基)-2-甲基哌嗪 (H-7) 处理，诱导具有神经元细胞表型特征的细胞，以及蛋白激酶 C 的同工酶模式

Mitsunobu Sato: "Differentiation therapy for salivary gland tumors" Japanese Journal of Cancer and Chemotherapy. 20. 1028-1036 (1993)

Mitsunobu Sato：“唾液腺肿瘤的分化治疗”日本癌症与化疗杂志。