Hölzel F, Albrecht M, Simon W E, Hänsel M, Metz R, Schweizer J, Dietel M
J Cancer Res Clin Oncol. 1985;109(3):217-26. doi: 10.1007/BF00390361.
Procedures for the in vitro determination of the drug-induced inhibition of mammary and ovarian carcinoma cell growth were established. In monolayer cultures derived from advanced tumors, separation of epithelial carcinoma cells from concomitant cells of fibroblast-like or mesothelial appearance was achieved by differential trypsinization. The carcinoma cell character of the stock cultures was verified by chromosome analyses showing a high degree of aneuploidy for the epitheloid cell lines and euploidy for cells of apparently mesenchymal origin. When cultured carcinoma cells were injected in nu/nu mice, the tissue and cell cultures obtained from the heterotransplantation tumors closely resembled the original tumors and cell cultures in morphology, karyotype, and expression of tumor markers. The action of carcinostatic drugs in the logarithmic phase of the carcinoma cell proliferation was tested by kinetics experiments in multiple experimental cultures. In cell proliferation assays based on cell counts the 50% inhibition dose (ID50) of the drug effects was determined from the dose-response curves. Comparison of the ID50s revealed highly differential effectiveness of the drugs examined. The inhibitory effects were reproducible, rendering the procedures used suitable for testing the chemosensitivity of newly explanted gynecological carcinoma cells by proliferation assays.
建立了体外测定药物诱导的乳腺癌和卵巢癌细胞生长抑制的方法。在源自晚期肿瘤的单层培养物中,通过差异胰蛋白酶消化将上皮癌细胞与成纤维细胞样或间皮样外观的伴随细胞分离。通过染色体分析验证了原代培养物的癌细胞特征,结果显示上皮样细胞系高度非整倍体,而明显间充质来源的细胞为整倍体。将培养的癌细胞注射到裸鼠中时,从异种移植肿瘤获得的组织和细胞培养物在形态、核型和肿瘤标志物表达方面与原始肿瘤和细胞培养物非常相似。通过在多个实验培养物中的动力学实验测试了抗癌药物在癌细胞增殖对数期的作用。在基于细胞计数的细胞增殖测定中,从剂量反应曲线确定药物作用的50%抑制剂量(ID50)。ID50的比较揭示了所检测药物的高度差异有效性。抑制作用是可重复的,使得所使用的方法适用于通过增殖测定来测试新移植的妇科癌细胞的化学敏感性。