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化疗药物对转染MDR-1基因的卵巢癌细胞株的作用
Relationship of Ovarian Cancer Cell Line Containing MDR1 Gene with Chemotherapy Regimens
【摘要】 通过将MDR-1基因(multidrugresistancegene)转染入卵巢癌细胞株AO及3AO后,探索化疗药物依托伯甙(etoposide,VP16)的药物敏感性,进一步了解卵巢癌细胞株、化疗药物及耐药性之间的关系。方法应用脂质体作为载体将MDR-1cDNA导入卵巢癌细胞株AO及3AO,转染后48h加入不同浓度的VP-16(1×10-5mg/μl、1×10-4mg/μl、1×10-3mg/μl),加药后在37℃含5%CO2的培养箱内培养48h,然后加入3H胸苷嘧啶,18h后测定3H-胸苷嘧啶掺入量cpm值。结果随着VP-16浓度的增加,AO细胞株的3H-胸苷嘧啶掺入量降低,而带有MDR-1基因的AO细胞株的3H-胸苷嘧啶掺入量与VP16浓度无关,其掺入量在中浓度及高浓度的VP-16中均高于AO细胞株,其差异经t检验,P<0.005及P<0.05。在3AO细胞株,转染了MDR-1基因的细胞3H-胸苷嘧啶掺入量降低(P<0.001)。随着VP-16浓度的增加,3AO细胞株及带有MDR-1基因的3AO细胞株的3H-胸苷嘧啶掺入降低,但带有MDR1基因的3AO细胞株的3H胸苷嘧啶掺入量在中浓度及高?
【Abstract】 Purpose To explore the effects of multidrug resistance gene (MDR1) transfection into human ovarian cancer cell lines AO and 3AO on sensitivity to chemotherapeutic agent Etoposide(VP16) in order to know the relationship of cancer cell line,chemotherapeutic agent and drug resistance . Methods (1)MDR1 cDNA was introduced into AO and 3AO cells using lipofection.(2)Cellular culture:After transgene,48 hours later,antineoplastic VP16 was added to the cell culture.After an additional 48 hours of cell culture in 5% CO 2 at 37℃, 3Hthymidine was added.18 hours later, 3 Hthymidine uptake was determined. Results Following the concentration of VP 16 increasing, AO cells showed a dose dependent decrease in 3 H thymidine uptake.But AOMDR 1 cells showed a dose dependent decrease in 3 H thymidine uptake. 3H thymidine uptake was high in AO MDR 1 cells than AO cells at mo-derate and high concentration of VP 16( P <0.005, P <0.05).In 3AO cell lines,3AO MDR 1 cells showed a decrease in 3H thymidine uptake( P <0.001).Following the concentration of VP 16 increasing,3AO cells and 3AO MDR 1 cells showed a dosedependent decrease in 3H thymidine uptake.But 3H thymidine uptake was higher in 3AO MDR 1 cells than 3AO cells at moderate and high concentration of VP 16( P <0.05, P <0.001). Conclusions AO or 3AO cells transfected MDR 1cDNA may appear cells biologic activated change.MDR 1 gene expression,cell’s type,chemotherapeutic agent and the dose of agent may influence chemosensitivity.
【Key words】 ovarian cancer cell; multidrug resistance gene; transfer; chemotherapy; chemosensitivity;
- 【文献出处】 上海医科大学学报 ,JOURNAL OF SHANGHAI MEDICA(UNIVERSITY) , 编辑部邮箱 ,1999年S1期
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