Angioli R, Janicek M, Sevin B, Estape R, Averette H, Koechli O, Untch M, Penalver M
MAYO CLIN JACKSONVILLE,DEPT OBSTET & GYNECOL,JACKSONVILLE,FL 32224. UNIV ZURICH,DEPT OBSTET & GYNECOL,ZURICH,SWITZERLAND. UNIV MUNICH GROSSHADERN,DEPT OBSTET & GYNECOL,MUNICH,GERMANY.
Int J Oncol. 1997 Oct;11(4):777-80. doi: 10.3892/ijo.11.4.777.
Lonidamine (LND), an indazole-3-carboxylic-acid derivative, is a new, relatively non-toxic, chemotherapeutic agent. LND, which interferes with energy metabolism, has been shown to potentiate the antineoplastic effects of chemotherapeutic agents and radiation. In this study, we evaluated the effect of LND in combination with cisplatin (DDP) or carboplatin (CARBO) on platinum resistant ovarian cancer cells. The ovarian cancer cell line BG-1 was selected as platinum resistant cell line, defined as cell line with survival fraction >50% at 0.5 peak plasma concentration (PPC). Cells were treated during the proliferative phase of cell growth with DDP and CARBO using doses between 0.1 and 1x (x = PPC). PPC of DDP = 2.5 mu g/ml, PPC of CARBO = 28 mu g/ml. Cells were also treated with LND at doses varying between 10 and 100 mu g/ml (PPC 20-50 mu g/ml). Drugs were used as single agents and in combination. Experiments were performed by treating the cells with DDP or CARBO for 90 min and with LND continuous exposure or 90 min only. The ATP cell viability assay was used to assess the antiproliferative effect of the drugs tested. Experiments were repeated at least 3 times. The synergistic interaction formula for anticancer agents and the t-test were used for the analysis of the results. LND was shown to be effective when used in continuous exposure only (IC50 = 0.58). The IC50 of DDP was 1.1 and the IC50 of CARBO was 0.64. Significant dose related antiproliferative effect of LND alone, as well as DDP and CARBO cytotoxicity potentiation was observed (p<0.05). LND was shown to have synergistic effect when combined with platinum compounds to treat ovarian cancer cells at doses of 20 and 30 mu g/ml. These doses are achievable in patients. LND, a relatively new antineoplastic agent with good clinical tolerance, has been shown to synergistically potentiate the antiproliferative effect of platinum compounds on platinum resistant ovarian cancer cells. LND is an agent of potential use for the treatment of ovarian cancer patients in combination with DDP or CARBO.
氯尼达明（LND）是一种吲唑 - 3 - 羧酸衍生物，是一种新型的、相对无毒的化疗药物。LND可干扰能量代谢，已被证明能增强化疗药物和放疗的抗肿瘤作用。在本研究中，我们评估了LND与顺铂（DDP）或卡铂（CARBO）联合使用对铂耐药卵巢癌细胞的影响。卵巢癌细胞系BG - 1被选为铂耐药细胞系，定义为在0.5倍血浆峰值浓度（PPC）下存活分数>50%的细胞系。在细胞生长的增殖期，用DDP和CARBO处理细胞，使用的剂量在0.1至1x（x = PPC）之间。DDP的PPC = 2.5μg/ml，CARBO的PPC = 28μg/ml。细胞还用剂量在10至100μg/ml（PPC 20 - 50μg/ml）之间的LND处理。药物单独使用或联合使用。通过用DDP或CARBO处理细胞90分钟以及用LND持续暴露或仅暴露90分钟来进行实验。使用ATP细胞活力测定法评估所测试药物的抗增殖作用。实验至少重复3次。使用抗癌药物的协同相互作用公式和t检验对结果进行分析。结果显示，仅在持续暴露时LND有效（IC50 = 0.58）。DDP的IC50为1.1，CARBO的IC50为0.64。观察到LND单独具有显著的剂量相关抗增殖作用，以及DDP和CARBO细胞毒性增强作用（p<0.05）。当LND与铂化合物联合使用，以20和30μg/ml的剂量处理卵巢癌细胞时，显示出协同作用。这些剂量在患者中是可以达到的。LND是一种相对较新的抗肿瘤药物，具有良好的临床耐受性，已被证明能协同增强铂化合物对铂耐药卵巢癌细胞的抗增殖作用。LND是一种可与DDP或CARBO联合用于治疗卵巢癌患者的潜在药物。
