Tsuruo T, Fidler I J
Cancer Res. 1981 Aug;41(8):3058-64.
Eradication of drug-resistant tumor foci is essential to the successful treatment of metastasis with chemotherapeutic agents. In this study, we examined the in vitro sensitivity to a variety of chemotherapeutic agents of tumor cells from parental tumors, from their in vitro-cloned populations, and from their spontaneous metastases. Three murine tumors were studied: the B16 melanoma; the K-1735 melanoma; and the UV-2237 fibrosarcoma. In addition, we also examined the in vitro drug sensitivity of cells from the A-375 human melanoma and its various subpopulations. The drugs used in these studies were Adriamycin, 4'-(9-acridinylamino)methanesulfon-m-anisidine, bleomycin, 5-)3,3-dimethyl-1-triazeno)imidazole-4-carboxamide, vincristine, and vindesine. The growth-inhibiting activity of the drugs was recorded in values which were derived from plotting the logarithm of the drug concentration versus the growth rate (percentage of control) of the treated cells and which determined the molar concentration of drugs necessary to reduce doubling by 50%. Our results demonstrate that differences in drug response exist among cells populating a parental tumor (in vitro cloned), between the parental line and its metastatic subpopulations (in vivo-selected lines), and among the various spontaneous metastases. These extensive differences in drug sensitivity could have profound implications for the treatment of metastases with cytotoxic drugs.
根除耐药性肿瘤病灶对于使用化疗药物成功治疗转移瘤至关重要。在本研究中，我们检测了来自亲代肿瘤、其体外克隆群体及其自发转移灶的肿瘤细胞对多种化疗药物的体外敏感性。研究了三种小鼠肿瘤：B16黑色素瘤、K - 1735黑色素瘤和UV - 2237纤维肉瘤。此外，我们还检测了A - 375人黑色素瘤及其不同亚群细胞的体外药物敏感性。这些研究中使用的药物有阿霉素、4'-（9 - 吖啶基氨基）甲磺酰间茴香胺、博来霉素、5 -（3,3 - 二甲基 - 1 - 三氮烯）咪唑 - 4 - 甲酰胺、长春新碱和长春地辛。通过绘制药物浓度对数与处理细胞生长速率（相对于对照的百分比）的关系图得出数值，记录药物的生长抑制活性，这些数值确定了使细胞倍增减少50%所需的药物摩尔浓度。我们的结果表明，在构成亲代肿瘤（体外克隆）的细胞之间、亲代细胞系与其转移亚群（体内选择的细胞系）之间以及各种自发转移灶之间存在药物反应差异。这些药物敏感性的广泛差异可能对用细胞毒性药物治疗转移瘤具有深远影响。
