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.

我们研究了间隙连接界细胞间通信（GJIC）对食管癌细胞系中抗癌药物（多西他）细胞毒性作用的作用。RT-PCR和Western印迹分析表明，人类食管癌细胞系KE-10，KE-10，KE-10，没有任何粘蛋白（CX）和GJIC能力的表达。 CX32基因被转染到细胞中。用CX32转染的细胞中的RT-PCR，Western印迹和免疫组织化学证实了CX32的表达（KE-10/CX32）。 KE-10/CX32显示了用染料转移测定法的GJIC容量的恢复，与KE-10相比，染料毒性提高了30-40％。在KE-10/C32细胞中，凋亡被上调。 MDR基因负责多西他赛的耐药性，并未在两种细胞系中表达。最后，我们研究了GJIC抑制剂Carbenoxolone对多西他赛细胞毒性作用的影响。甲氧醇酮将KE-10/CX32细胞中多西他赛的细胞毒性降低了20％。这些日期表明GJIC参与多西他赛的细胞毒性作用。