Differential cytotoxic effects of docetaxel in a range of mammalian tumor cell lines and certain drug resistant sublines in vitro

摘要: Thein vitro cytotoxic effects of docetaxel (Taxotere®; RP56976, NSC688503) proved both time and concentration dependent. Amongst thirteen human cell lines from various tumor types, exposure to increasing concentrations over 24 hrs resulted in a plateau-shaped dose response curve, suggesting that increased kill becomes more dependent on duration than concentration. IC50 (reducing survival by 50%) ranged 0.13–3.3 ng/ml, with three neuroblastoma proving most sensitive breast two colon carcinoma showing least sensitivity. There was significant cross-resistance the classic multidrug resistant (MDR) Chinese hamster ovarian (CHO) CHRC5 line lymphoblastoid CCRF-CEMVLB1000 line, as well vincristine(VCR)-selected MDR MCF-7 sublines. All four these sublines overexpress P-glycoprotein (Pgp), did 6fold docetaxel-selected CHO subline. As an apparent corollary, teratoma selected for etoposide resistance some VCR expressing low levels resistance, yet all Pgp positive, no crossresistance identified. Verapamil modulated only drug overexpressing Pgp. Four other 5-fluorouracil, cisplatin or teniposide, showed lack docetaxel. Furthermore, not apparant epipodophyllotoxin-selected alterations topoisomerase II, indicating its effectiveness against cells II-related phenotype. Our observation automatically expressed tumour appears interest potential clinical relevance.