Development of targeting therapy using specific difference of lipid composition of oral cancer cell, resistant

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13672098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: HIROSHIMA UNIVERSITY
• Principal Investigator: TORATANI Shigeaki University Dental Hospital, Assistant Professor, 歯学部附属病院, 講師 (90172220)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Tetsuji Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00169153)
• Project Period (FY): 2001 – 2002
• Keywords: resistant cancer cells / anti-cancer drugs / drug resistant related gene / squamous cell carcinoma / carcinoma of salivary gland / lipid composition of cell membrane / liposome

Research Abstract

On the treatment of malignant tumor, it has been known that chemotherapy using of anti-cancer drugs is useful to suppression the recurrence and metastasis of cancer. Although we encounter several cases that can not obtain enough treatment effects of chemotherapy on tumors of recurrence and metastasis, because of acquirement resistance against anti-cancer drugs after chemotherapy. We attempted to construct a drug delivery system using a liposome entrapped anti-cancer drugs which is comparable to lipid composition of cell membrane squamous cell carcinoma cell (SCC) and salivary gland carcinoma cell lines(SAC). Three resistant cell lines, NA-ADM, NA-CDDP and HSY-CDDP, are established from NA of SCC and HSY of SAC agaist cisplatin(CDDP) and adriamycin (ADM). Of the cell lines tested. NA-ADM. NA-CDDP and HSY-CDDP have shown to be less sensitive to CDDP and ADM compare to parent cell lines in serum-free culture method. To elucidate the mechanism of resistance against anti-cancer drugs, expression of drug resistant related genes, p-glycoprotein (MDR-1), multi-drug resistant related (MRP) -1, -2, and -3, and glutathione S- transferase, were examined by quantative reverse transcription polymerase chain reaction (RT-PCR) method. As the result, the expression of MRP-2 gene exhibited high level on NA-CDDP and HSY-CDDP, and the expression of p-glycoprotein gene show high level on NA-ADM. Although there was no difference of lipids composition of cell membranes between resistant cell lines and parent cell lines.