Petru E, Sevin B U, Perras J, Boike G, Ramos R, Nguyen H, Averette H E
Department of Obstetrics and Gynecology, School of Medicine, University of Miami, Florida 33101.
Gynecol Oncol. 1990 Aug;38(2):155-60. doi: 10.1016/0090-8258(90)90032-g.
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 greater than or equal to 50% cell kill at 0.5 x peak plasma concentration as compared to controls. For 4-OH-CTX and ARA-C, 3 and 0.5 micrograms/ml were chosen as 0.5 x 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.
顺铂(DDP)和环磷酰胺常用于治疗卵巢癌;然而,患者生存率仍然很低。使用ATP分析法研究了标准抗肿瘤药物DDP、4-氢过氧环磷酰胺(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)对四种代表性卵巢癌细胞系的细胞毒性程度,该方法可测定细胞总杀伤情况。来自经预处理和未经预处理患者的CAOV-3、OVCAR-3、SKOV-3和BG-1细胞系,分别暴露于六种不同浓度的药物中90分钟。在第7天,测定细胞内ATP含量。敏感性定义为与对照组相比,在0.5倍血浆峰值浓度时细胞杀伤率大于或等于50%。对于4-OH-CTX和ARA-C,分别选择3微克/毫升和0.5微克/毫升作为0.5倍参考值。对于每种细胞系中的每种药物,均观察到高度可重复的剂量反应关系。CAOV-3细胞对除DDP、ARA-C和IF之外的所有药物敏感,OVCAR-3细胞对除DDP和IF之外的所有药物敏感。SKOV-3细胞对除VCR之外的所有药物耐药,BG-1细胞对除MITOM C和5-FU之外的所有药物耐药。上述细胞系中观察到的对抗肿瘤药物的明显异质性反应,突出了在治疗前评估个体患者敏感性概况的重要性。