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

Research Project

Project/Area Number	09672085
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Surgical dentistry
Research Institution	Hyogo Collge of Medicine
Principal Investigator	TAKAHASHI Yumiko Hyogo Collge of Medicine, School of Medicine, Associate, 医学部, 助手 (70278836)
Co-Investigator(Kenkyū-buntansha)	URADE Masahiro Hyogo Collge of Medicine, School of Medicine, Professor and Chair, 医学部, 教授 (70104883)
Project Period (FY)	1997 – 1998
Project Status	Completed (Fiscal Year 1998)
Budget Amount *help	¥2,500,000 (Direct Cost: ¥2,500,000) Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords	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)
Research Abstract	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.