Study on the mechanism of the cis-platin resistance of the oral squamous cell carcinoma

口腔鳞癌顺铂耐药机制研究

• 批准号: 09672085
• 负责人: TAKAHASHI Yumiko
• 金额: $ 1.6万
• 依托单位: Hyogo Collge of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672085/
• 关键词: oral squamous cell carcinoma; CDDP-resistance; intracellular Pt content; P-glycoprotein; glutathione (GSH); glutathione S-transferase (GST)-pi; heat shock protein (HSP); metallothionein (MT); CDDP細胞内蓄積量; HSP(熱ショック蛋白)

This study was designed to analyze the mechanism of cis-platin (CDDP) resistance of the oral squamous cell carcinoma.1. The establishment of CDDP resistant oral squamous cell carcinoma cell line. We established the CDDP resistant KB-CDDPr cell line from KB cells, gradually increasing CDDP concentration in medium. KB-CDDPr showed cross-resistant to MMC, CBDDCA, 5-FU and BLM.2. The comparison between KB-CDDPr and parental KB concerning intracellular Pt content, P-glycoprotein, glutathIone (GSH), glutathione S-transferase ( GST )-pi, heat shock protein (HSP) and metallothionein (MT).1)The intracelluler Pt content of KB-CDDPr and KB increased dose-and time-dependently, and the Pt content of KB-CDDPr was as 1/3 as that of KB.2)The both cell lines were negative in the staining of imrnunohistocemlstry of P-glycoprotein.3)There was no significant difference between both cells of the volumes of GSH irrespective of CDDP treatment.4)There was no significant difference between both cells in the immunohIstochemical staining, the levels of protein nor the levels of mRNA of GST-2pi Irrespective of CDDP treatment.5)The immunohistochemical staining of HSP27 showed more positive in KB-CDDPr, treated with CDDP furthermore. That of HSP50 showed strongly positive In both cell lines. That of HSP7O showed the same as that of HSP27.6)There was no significant difference between both cells in the staining ofthe imunohlstochemistry of MT irrespective of CDDP treatment.From these findings, it was indicated that intracellular Pt content and HSP27 and HSP7O were involved in the resistance of CDDP of KB-CDDPr.

本研究旨在分析口腔鳞状细胞癌顺铂耐药的机制。耐CDDP口腔鳞状细胞癌细胞系的建立。我们从KB细胞中逐渐增加培养基中CDDP的浓度，建立了抗CDDP的KB- cddpr细胞系。KB-CDDPr对MMC、CBDDCA、5-FU和BLM.2具有交叉抗性。KB- cddpr与亲本KB细胞内Pt含量、p -糖蛋白、谷胱甘肽（GSH）、谷胱甘肽s -转移酶(GST)-pi、热休克蛋白（HSP）和金属硫蛋白（MT）的比较1) KB- cddpr和KB细胞内Pt含量呈剂量和时间依赖性增加，KB- cddpr细胞内Pt含量为KB的1/3。2)两株细胞系p -糖蛋白免疫组化染色均为阴性。3)无论CDDP处理方式如何，两种细胞间GSH体积均无显著差异。4)两种细胞在免疫组化染色、蛋白水平和GST-2pi mRNA水平上均无显著差异，与CDDP处理无关。5) HSP27免疫组化染色在KB-CDDPr组中呈阳性，CDDP组进一步升高。HSP50在两种细胞系中均呈强阳性。hsp70细胞与HSP27.6细胞的免疫组化染色无显著差异，与CDDP处理无关。由此可见，细胞内Pt含量和HSP27、hsp70参与了KB-CDDPr对CDDP的耐药。

项目成果

高橋由美子: "抗癌剤耐性とHSP" 組織培養工学. 23(4). 127-132 (1997)

高桥由美子：“抗癌药物耐药性和 HSP”组织培养工程 127-132（1997）。

高橋由美子、浦出雅裕: "抗癌剤耐性とHSP" 組織培養工学. 23(4). 127-132 (1997)

Yumiko Takahashi，Masahiro Urade：“抗癌耐药性和 HSP”组织培养工程 127-132（1997）。