The Mechanism Study of Multi-Drug Resistance (MDR) in Human Brain Malignant Tumor Cell Lines

• Main Authors: Yueh, Kuo-Chu, 樂國柱
• Other Authors: 李偉華
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/69073080952519430133

碩士 === 國防醫學院 === 病理及寄生蟲學研究所 === 85 === Glioblastoma multiforme (GBM), a high-grade malignant brain tumor, has less than 10% of two-year survival rate. It owns a poor prognosis by current surgery, radiotherapy or chemotherapy, so it is important to find new therapy methods to cope with this malignancy. The purpose of this study is to investigate the possible mechanisms of Multi-Drug Resistance (MDR) of primary brain tumors by measurement of cellular P-glycoprotein, lung resistance-related protein (LRP), multidrug resistance-associated protein (MRP), DNA topoisomerase II (Topo II), glutathion S-transferase pi (GST-π) and apoptosis related proteins (bcl-2, Bax, p53, ras). Furthermore, we prospected to find out the relationship between protein kinase C (PKC) isoforms contents and multi-drug resistance, and the role of PKC modulators in anticancer drug cytotoxicity. The results reveal these human brain GBM cell lines are sensitive to adriamycin, vinblastine, and vincristine. Human brain malignant tumor cell lines (GBM8401, GBM8804, GBM8909, BT9201. and IOMM-Lee) have higher expression of P-glycoprotein, glutathione and apoptosis related proteins, but lower expression of topoisomerase II mRNA. Three (75%) of four glioblastoma multiforme cell lines (GBM8401, GBM8804, GBM8909) have expression of lung resistancerelated protein (LRP). The PKC expression is not related to MDR although the modulators of PKC have prominant relationship to the intake of anticancer drug (adriamycin) and PKC content. These results reveal the possibility of co-expression of multiple mechanisms of multidrug resistance in human brain tumor cell lines. However, we detect higher expression of p-glycoprotein, but the drug resistance expression to anticancer drug is not compatible with P-glycoprotein related MDR. Because expression of MDR phenotype in primary malignant brain tumor seems apt to poor response of chemotherapy, we suggest that rule out all the factors involved in the MDR mechanism will get excellent therapeutic effects before you choice which chemotherapeutic protocol for any brain tumor.