Combinational effect of topotecan and octreotide on murine leukemia cells in vivo and in vitro.
OBJECTIVE
The activity of topotecan (TPT) against a number of hematological malignancies is now notably increased. TPT is a drug which inhibits the DNA enzyme topoisomerase I (topo I), thereby leading to the induction of tumor cell apoptosis. On the other hand, octreotide (OCT) is a synthetic analogue of somatostatin, which can induce apoptosis and antiproliferative effects on various human tumor cell lines, human xenografts and animal tumors, as well as on lymphoproliferative neoplasms. Hereby, we studied the effects of TPT and OCT, and their combination in the treatment of the rodent P388 lymphocytic leukemia, in vitro and in vivo.


METHODS
Cell cultures of P388 lymphocytic leukemia cells, as well as BDF1 male and female mice implanted with the P388 leukemia cells, were used for the in vitro and in vivo evaluation of the antineoplastic activity of OCT and TPT.


RESULTS
A significant increase of antileukemic activity of the combined treatment with both TPT and OCT was demonstrated. These results suggest that OCT enhances the effectiveness of TPT in the treatment of leukemia.


CONCLUSIONS
Our results indicate that the combination of OCT with TPT in the treatment of hematological neoplasias is effective, and represents an interesting addition to the future therapeutic options, because os its mechanism of action and its toxicity profile.
Dalezis
P
P
Laboratory of Cell Culture - Molecular Modeling & Drug Design, Symeonidio Research Center, Theagenio Cancer Hospital, Thessaloniki, Greece.
Geromichalos
G D
GD
Voyatzi
S
S
Trafalis
D
D
Athanassiou
A E
AE
Koutsilieris
M
M
Papageorgiou
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D007941:Leukemia P388 / Q000473:pathology*; D008297:Male; D051379:Mice; D015282:Octreotide / Q000008:administration & dosage* / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000008:administration & dosage* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D015282:Octreotide