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

利用口腔癌细胞脂质成分的特异性差异开发靶向治疗，耐药

• 批准号: 13672098
• 负责人: TORATANI Shigeaki
• 金额: $ 2.62万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672098/
• 关键词: resistant cancer cells; anti-cancer drugs; drug resistant related gene; squamous cell carcinoma; carcinoma of salivary gland; lipid composition of cell membrane; liposome; 唾液腺癌; 膜脂質組成; 扁平上皮癌細; 唾液腺由来腺癌細胞

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.

在治疗恶性肿瘤时，众所周知，使用抗癌药物的化学疗法可用于抑制癌症的复发和转移。尽管我们遇到了几种病例，这些病例无法获得化学疗法对复发和转移肿瘤的足够的治疗作用，但由于化学疗法后对抗癌药物的耐药性。我们尝试使用脂质体滞留的抗癌药物来构建药物输送系统，该药物与细胞膜鳞状细胞癌细胞（SCC）和唾液腺癌细胞（SAC）的脂质组成相当。从SAC Agaist顺铂（CDDP）和Adriamycin（ADM）建立了三种抗性细胞系，Na-ADM，Na-CDP和HSY-CDP。测试的细胞系。 na-adm。 Na-CDDP和HSY-CDP已证明对CDDP不太敏感，ADM与无血清培养方法中的母细胞系相比。为了阐明对抗癌药物的耐药性的机制，通过定量逆转录聚合酶链反应（RT-PCR）方法检查了耐药相关基因，P-糖蛋白（MDR-1），P-糖蛋白（MDR-1），多药耐药相关（MRP）-1，-2和-3和谷胱甘肽S-转移酶的表达。结果，MRP-2基因的表达在Na-CDDP和HSY-CDP上表现出很高的水平，并且P-糖蛋白基因的表达在Na-ADM上表现出很高的水平。尽管抗性细胞系和母细胞系之间的细胞膜脂质组成没有差异。