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

在恶性肿瘤的治疗上，已经知道使用抗癌药物进行化疗对抑制肿瘤的复发和转移是有用的。虽然我们遇到过几例由于化疗后对抗癌药物的获得性耐药，化疗对复发转移的肿瘤不能获得足够的治疗效果。我们试图用脂质体包裹抗癌药物构建一个与细胞膜鳞状细胞癌细胞（SCC）和唾液腺癌细胞系（SAC）的脂质组成相当的药物传递系统。以SCC的NA和SAC的HSY为基础，建立了3株抗顺铂（CDDP）和阿霉素（ADM）的耐药细胞株NA-ADM、NA-CDDP和HSY-CDDP。测试的细胞系。NA-ADM。与亲本细胞系相比，NA-CDDP和HSY-CDDP对CDDP和ADM的敏感性较低。为阐明耐药机制，采用定量逆转录聚合酶链式反应（RT-PCR）方法检测耐药相关基因p-糖蛋白（MDR-1）、多重耐药相关基因(MRP) -1、-2、-3和谷胱甘肽S-转移酶的表达。结果表明，MRP-2基因在NA-CDDP和HSY-CDDP上高表达，p-糖蛋白基因在NA-ADM上高表达。抗性细胞系与亲本细胞系细胞膜脂质组成无明显差异。

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.