Willson J K, Long B H, Marks M E, Brattain D E, Wiley J E, Brattain M G
Cancer Res. 1984 Dec;44(12 Pt 1):5880-5.
A human colon carcinoma cell line resistant to mitomycin C (MMC) was obtained by repeated exposure of a previously described sensitive parental line, HCT 116, to MMC in vitro. Xenografts grown from the MMC-resistant phenotype were not inhibited in MMC-treated animals, while MMC treatment produced growth inhibition in parental cell xenografts. The MMC-resistant phenotype exhibited a greater amount of a Mr 148,000 cell surface protein than did the parental line. The increase in this Mr 148,000 cell surface protein correlated positively with the degree of MMC resistance. Alkaline elution of filter-bound DNA from resistant cells exposed to MMC in vitro showed a decrease in DNA cross-link formation such that a 10-fold higher MMC concentration was required to produce similar cross-link formation in the resistant cell as compared to the parental cell. The development of MMC resistance was not associated with in vitro cross-resistance to other natural product cytotoxic drugs. This model for resistance to MMC will be useful in future studies to define the mechanisms for MMC action and resistance in human colon carcinoma cells.
通过将先前描述的敏感亲代细胞系HCT 116在体外反复暴露于丝裂霉素C（MMC），获得了一株对MMC耐药的人结肠癌细胞系。由MMC耐药表型生长而来的异种移植瘤在接受MMC治疗的动物中未受到抑制，而MMC治疗对亲代细胞异种移植瘤产生了生长抑制作用。与亲代细胞系相比，MMC耐药表型的细胞表面有更多分子量为148,000的蛋白质。这种分子量为148,000的细胞表面蛋白的增加与MMC耐药程度呈正相关。体外将耐药细胞暴露于MMC后进行碱性洗脱，结果显示DNA交联形成减少，因此与亲代细胞相比，耐药细胞需要10倍更高浓度的MMC才能产生相似的交联形成。MMC耐药的产生与对其他天然产物细胞毒性药物的体外交叉耐药无关。这种MMC耐药模型将有助于未来研究确定人结肠癌细胞中MMC作用和耐药的机制。
