COMPARATIVE CHEMOSENSITIVITY PROFILES IN 4 HUMAN OVARIAN-CARCINOMA CELL-LINES MEASURING ATP BIOLUMINESCENCE

COMPARATIVE CHEMOSENSITIVITY PROFILES IN 4 HUMAN OVARIAN-CARCINOMA CELL-LINES MEASURING ATP BIOLUMINESCENCE
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DOI:
10.1016/0090-8258(90)90032-g
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发表时间:
1990-08-01
影响因子:
4.7
通讯作者:
AVERETTE, HE
AVERETTE, HE
中科院分区:
医学2区
文献类型:
--
作者:
PETRU, E;SEVIN, BU;AVERETTE, HE

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顺铂(DDP)和环磷酰胺是治疗卵巢癌的常用药物,但存活率仍然很低。采用三磷酸腺苷(ATP)比色法研究了顺铂(DDP)、4-羟基环磷酰胺(4-OH-CTX)、丝裂霉素C(MITOM C)、长春新碱(VCR)、依托泊苷(VP-16)、5-氟尿嘧啶(5-FU)、阿糖胞苷(ARA-C)和干扰素(IF)对4种典型卵巢癌细胞株的细胞毒作用。细胞株CAOV-3、OVCAR-3、SKOV-3和BG-1分别来自治疗前和未治疗的患者,暴露于6种不同浓度的90分钟。第7天进行细胞内三磷酸腺苷测定。敏感度定义为0.5倍时50%的细胞杀伤率。与对照组相比,峰值血浆浓度。对于4-OH-CTX和ARA-C,选择3和0.5微克/毫升为0.5倍。参考值。对于每种细胞系中的每种药物,都观察到了高度重复性的剂量-反应关系。CAOV-3细胞对除DDP、ARA-C和IF外的所有药物均敏感,OVCAR-3细胞对除DDP和IF外的所有药物均敏感。SKOV-3细胞对除长春新碱外的所有药物耐药,BG-1细胞对除MITOM C和5-FU外的ALL耐药。在上述细胞系中观察到的对抗肿瘤药物的明显异质性反应强调了在治疗前评估个别患者的敏感性的重要性。
cis-Platinum (DDP) and cyclophosphamide are commonly used for the treatment of ovarian cancer; however, survival remains poor. The degree of cytotoxicity of the standard antineoplastic agents DDP, 4-hydroperoxy-cyclophosphamide (4-OH-CTX), mitomycin C (MITOM C), vincristine (VCR), etoposide (VP-16), 5-fluorouracil (5-FU), cytosine arabinoside (ARA-C), and interferon (IF) in four representative ovarian cancer cell lines was studied using the ATP assay, which measures total cell kill. Cell lines CAOV-3, OVCAR-3, SKOV-3, and BG-1, which were derived from both pretreated and untreated patients, were exposed to six different concentrations for 90 min. On Day 7, intracellular ATP determinations were done. Sensitivity was defined as .gtoreq.50% cell kill at 0.5 .times. peak plasma concentration as compared to controls. For 4-OH-CTX and ARA-C, 3 and 0.5 .mu.g/ml were chosen as 0.5 .times. reference values. For each drug in each cell line, a highly reproducible dose-response relationship was observed. CAOV-3 cells were sensitive to all drugs except DDP, ARA-C and IF, and OVCAR-3 cells to all except DDP and IF. SKOV-3 cells were resistant to all agents except VCR, and BG-1 cells to all except MITOM C and 5-FU. The apparent heterogeneic response to antineoplastic agents observed in the above cell lines underscores the importance of assessing individual patients'' sensitivity profiles before treatment.