Dose enhancement effect of anticaner drugs associated with increased temperature in vitro.
OBJECTIVE
To evaluate in vitro the influence of elevated temperature (42 degrees C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine.


METHODS
HeLa tumor cell cultures, 24h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 degrees C or 42 degrees C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer.


RESULTS
Hyperthermia alone caused only 10-20% growth inhibition of cell culture. All the chemotherapeutic drugs used demonstrated a dose enhancement effect at elevated temperature. Thermal enhancement ratio for cell proliferation for oxaliplatin, vinorelbine, carboplatin and ifosfamide exceeded 4, for doxorubicin and gemcitabine exceeded 2. Thermal enhancement ratio for cell death did not exceed 1.4.


CONCLUSIONS
Synergism of hyperthermia and chemotherapeutical drugs was clearly demonstrated for oxaliplatin, vinorelbine, carboplatin, ifosfamide and to a lesser extent for doxorubicin and gemcitabine. Enhancement of the cytostatic effect of anticancer drugs by hyperthermia was more prominent than their cytotoxic effect.
Istomin
Yu P
YP
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk 223040, Belarus. istomin06@mail.ru
Zhavrid
E A
EA
Alexandrova
E N
EN
Sergeyeva
O P
OP
Petrovich
S V
SV
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006979:Hyperthermia, Induced; D007069:Ifosfamide / Q000008:administration & dosage / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077150:Oxaliplatin; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology; D013696:Temperature; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D016190:Carboplatin; D000077235:Vinorelbine; D007069:Ifosfamide; D000093542:Gemcitabine