Role of gap junctional intercellular communication on the cytotoxic effect of anticancer drug

间隙连接细胞间通讯在抗癌药物细胞毒作用中的作用

• 批准号: 16591377
• 负责人: TANAKA Toshiaki
• 金额: $ 2.05万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591377/
• 关键词: esophageal cancer; chemotherapy; gap junction; 制癌剤感受性; 抗癌剤耐性

We investigate the role of gap junctional intercellular communication(GJIC)on the cytotoxic effect of an anticancer drug, docetaxel, in esophageal cancer cell line.RT-PCR and Western blot analysis revealed that human esophageal cancer cell line, KE-10, didn't have expression of any connexin (Cx) and GJIC capacity. Cx32 gene was transfected into the cells. Cx32 expression was confirmed with RT-PCR, Western blot and immunohistochemisty in the Cx32-transfected cells (KE-10/Cx32). KE-10/Cx32 showed the restoration of GJIC capacity with dye transfer assay and the cyotoxicity was enhanced by 30-40% compared with KE-10. Apoptosis was upregulated in KE-10/C32 cells. And MDR gene, which is responsible for the drug resistance of docetaxel, wasn't expressed in two cell lines. Finally, we investigated the effect of the GJIC inhibitor, carbenoxolone, on cytotoxic effect of docetaxel. Carbenoxolone decreased the cytotoxity of docetaxel in KE-10/Cx32 cells by 20%. These date suggest that GJIC is involved in the cytotoxic effect of docetaxel.

我们研究了缝隙连接细胞间通讯(GJIC)在抗癌药物多西紫杉醇对食管癌细胞系的细胞毒作用中的作用。RT-PCR和Western印迹分析表明，人食管癌细胞系KE-10不表达任何连接蛋白(Cx)和GJIC能力。将Cx32基因导入细胞。RT-PCR、Western印迹和免疫组织化学检测证实Cx32基因在KE-10/Cx32细胞中有表达。染料转移实验显示KE-10/Cx32细胞的GJIC活性恢复，细胞毒作用较KE-10细胞提高30-40%。KE-10/C32细胞凋亡上调。而导致多西紫杉醇耐药的MDR基因在两种细胞系中均未表达。最后，我们研究了GJIC抑制剂Carbenoxolone对多西紫杉醇细胞毒作用的影响。Carbenoxolone使多西紫杉醇对KE-10/Cx32细胞的毒性降低20%。提示GJIC参与了多西紫杉醇的细胞毒作用。