Teicher B A, Herman T S, Holden S A, Wang Y Y, Pfeffer M R, Crawford J W, Frei E
Dana-Farber Cancer Institute, Boston, MA 02115.
Science. 1990 Mar 23;247(4949 Pt 1):1457-61. doi: 10.1126/science.247.4949.1457.
EMT-6 murine mammary tumors were made resistant to cis-diamminedichloroplatinum (II) (CDDP), carboplatin, cyclophosphamide (CTX), or thiotepa in vivo by treatment of tumor-bearing animals with the drug during a 6-month period. In spite of high levels of in vivo resistance, no significant resistance was observed when the cells from these tumors were exposed to the drugs in vitro. The pharmacokinetics of CDDP and CTX were altered in animals bearing the respective resistant tumors. The resistance of all tumor lines except for the EMT-6/thiotepa decreased during 3 to 6 months in vivo passage in the absence of drugs. These results indicate that very high levels of resistance to anticancer drugs can develop through mechanisms that are expressed only in vivo.
通过在6个月期间用药物治疗荷瘤动物，使EMT - 6小鼠乳腺肿瘤对顺二氯二氨铂（II）（CDDP）、卡铂、环磷酰胺（CTX）或噻替派产生体内抗性。尽管体内抗性水平很高，但当将这些肿瘤的细胞在体外暴露于药物时，未观察到明显的抗性。在携带相应抗性肿瘤的动物中，CDDP和CTX的药代动力学发生了改变。除EMT - 6/噻替派外，所有肿瘤系的抗性在无药物的情况下体内传代3至6个月期间均有所下降。这些结果表明，通过仅在体内表达的机制可产生对抗癌药物的极高抗性。
