Park J G, Kramer B S, Steinberg S M, Carmichael J, Collins J M, Minna J D, Gazdar A F
National Cancer Institute-Navy Medical Oncology Branch, Naval Hospital, Bethesda, Maryland 20814-5105.
Cancer Res. 1987 Nov 15;47(22):5875-9.
The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutic agents was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). Four of the cell lines were from primary tumors and seven from metastases. Eight lines were from patients with no prior chemotherapy. From assay results, we predict 5-fluorouracil (5-FU) to be the sole active agent of the seven tested. This is based on two observations: the range of drug concentrations which produced 50% inhibition of cell growth was greatest with 5-FU (388-fold versus 5- to 30-fold with the other six agents); and the area under the curve (AUC) which produced 50% growth inhibition was within a clinically achievable range only for 5-FU. Since the assay AUC of 5-FU at 50% inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity. In the best fitting model, sensitivity was positively correlated with cloning efficiency in media and with cell surface TAG-72 (a tumor-associated glycoprotein found on epithelial tumors of ovary, lung, colon, and breast origin) expression. If validated with an in vivo test such as the nude mouse model, the MTT assay could be very useful in new drug screening for colorectal carcinoma, for examining combination chemotherapy for synergy, for exploring strategies for biochemical modulation, and perhaps in individualizing therapy when cell lines can be established from a patient.
采用基于四氮唑盐的半自动比色法（MTT 法）测定了 11 种人结肠直肠癌细胞系对 7 种化疗药物的体外化学敏感性。其中 4 种细胞系来自原发性肿瘤，7 种来自转移瘤。8 种细胞系来自未接受过化疗的患者。根据检测结果，我们预测 5-氟尿嘧啶（5-FU）是所测试的 7 种药物中唯一具有活性的药物。这基于两点观察：产生 50%细胞生长抑制的药物浓度范围，5-FU 最大（388 倍，而其他六种药物为 5 至 30 倍）；产生 50%生长抑制的曲线下面积（AUC）仅 5-FU 在临床可达到的范围内。由于在 11 种细胞系中只有两种细胞系的 5-FU 在 50%抑制时的检测 AUC 在临床可达到范围内，我们进行了多变量分析以探索预测 5-FU 敏感性的参数。在最佳拟合模型中，敏感性与培养基中的克隆效率以及细胞表面 TAG-72（一种在卵巢、肺、结肠和乳腺来源的上皮肿瘤中发现的肿瘤相关糖蛋白）表达呈正相关。如果通过裸鼠模型等体内试验得到验证，MTT 法在结直肠癌新药筛选、检查联合化疗的协同作用、探索生化调节策略以及在能够从患者建立细胞系时可能用于个体化治疗方面可能会非常有用。
