Influence of gemcitabine (2',2'-difluoro-deoxycytidine) and 2-chlorodeoxyadenosine on growth of normal and leukemic cells in vitro.
The aim of the study was to investigate the influence of gemcitabine (2',2'-difluorodeoxycytidine, dFdC) used alone and in combination with 2-chlorodeoxyadenosine (2-CdA) on the colony growth of normal granulocyte-macrophage progenitor cells (CFU-GM) from 15 hematologically healthy donors as well as on CFU-GM from 15 chronic myelogenous leukemia (CML) patients in semisolid cultures in vitro. dFdC and 2-CdA were used either separately or in the following combinations of concentrations: (1) 0.25 nM of dFdC and 2.5 nM of 2-CdA; (2) 0.5 nM of dFdC and 5 nM of 2-CdA; (3) 1 nM of dFdC and 10 nM of 2-CdA; (4) 2 nM of dFdC and 20 nM of 2-CdA. We observed that both dFdC and 2-CdA used separately inhibited the growth of colonies formed by normal and CML CFU-GM cells in a dose-dependent manner. Moreover, the combined therapy with dFdC and 2-CdA caused statistically significant inhibition of the colony growth in both normal and CML CFU-GM cultures. In addition, the inhibition of CML CFU-GM colony formation was greater and statistically significant in the case of the combined therapy using higher concentrations of these drugs as compared with inhibition of the growth of normal CFU-GM colonies. These observations were the basis for the evaluation of the interaction type between dFdC and 2-CdA. We have shown that dFdC used in a combination with 2-CdA acts in an additive way on normal and CML CFU-GM cells.
Lech-Marańda
E
E
Department of Hematology, Medical University of Lódź, Poland.
Korycka
A
A
Robak
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D017338:Cladribine / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D017338:Cladribine; D000093542:Gemcitabine