Theodorescu D, Connors K M, Groce A, Hoffman R M, Kerbel R S
University of Toronto, Department of Surgery, Ontario, Canada.
Anticancer Res. 1993 Jul-Aug;13(4):941-6.
The mechanism of drug resistance in human cancers is complex. In addition to overexpression of a series of multiple-drug-resistance genes, there has been the suggestion that the Ha-ras gene may participate in conferring resistance. In this study, a series of three human-bladder carcinoma cell lines were studied, one parental type, one transfected by wild-type Ha-ras and another transfected by mutant Ha-ras. The ras gene was overexpressed in the latter two cell lines which also were more invasive than the parental when injected as individual cells in the nude-mouse bladder. The results described here have indicated that the ras-gene expression level or mutational status did not affect drug resistance when the tumor lines were histocultured as three-dimensional tissue on collagen-sponge-gels. The drug-response spectrum of the histocultured lines qualitatively reflected a clinical experience although all lines were relatively drug resistant, possibly reflecting their three-dimensional configuration in culture.
人类癌症中的耐药机制很复杂。除了一系列多药耐药基因的过表达外，还有研究表明Ha-ras基因可能参与赋予耐药性。在本研究中，对一系列三种人膀胱癌细胞系进行了研究，一种是亲本类型，一种用野生型Ha-ras转染，另一种用突变型Ha-ras转染。ras基因在后两种细胞系中过表达，当将其作为单个细胞注射到裸鼠膀胱中时，它们也比亲本细胞系更具侵袭性。此处描述的结果表明，当肿瘤细胞系在胶原海绵凝胶上作为三维组织进行组织培养时，ras基因表达水平或突变状态并不影响耐药性。组织培养细胞系的药物反应谱定性地反映了临床经验，尽管所有细胞系都相对耐药，这可能反映了它们在培养中的三维结构。
