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

在恶性肿瘤的治疗上，抗癌药物的化疗有助于抑制肿瘤的复发和转移。虽然我们遇到了一些复发和转移的肿瘤由于化疗后对抗癌药物产生耐药性而不能获得足够的化疗效果的病例。我们试图利用脂质体包裹抗癌药物，构建一种与细胞膜鳞状细胞癌细胞(SCC)和涎腺癌细胞系(SAC)的脂质组成相当的药物输送系统。用顺铂(CDDP)和阿霉素(ADM)分别从鳞癌NA和HSY建立了3个耐药细胞系NA-ADM、NA-CDDP和HSY-CDDP。在测试的细胞系中。NA-ADM。在无血清培养方法中，NA-CDDP和HSY-CDDP对CDDP和ADM的敏感性低于亲本细胞系。采用定量逆转录聚合酶链式反应方法检测耐药相关基因P-糖蛋白1、多药耐药相关基因1、2、3和谷胱甘肽S转移酶的表达，探讨其耐药机制。结果显示，mrp-2基因在NA-CDDP和HSY-CDDP中高表达，P-糖蛋白基因在NA-ADM中高表达。耐药细胞系与亲本细胞系细胞膜脂类组成无明显差异。

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.