Enhancement of cisplatin sensitivity and platinum uptake by 40 degrees C hyperthermia in resistant cells.
We studied the cytotoxic and pharmacological properties of 40 degrees C hyperthermia and CDDP in CDDP-sensitive (IMC-3) and CDDP-resistant (IMC-3-DDP) human maxillary carcinoma cells. Heating at 40 degrees C alone caused almost no cell killing to IMC-3 and IMC-3-DDP cells. In both cell lines, the dose-dependent cytotoxicity of 2-h exposures to CDDP was increased at 40 degrees C in comparison to 37 degrees C. Heating at 40 degrees C also potentiated CDDP cytotoxicity in both IMC-3 and IMC-3-DDP cells with thermal chemoenhancement ratios (CER) of 1.48 and 1.94, respectively. The intracellular CDDP uptake level of IMC-3-DDP at 37 degrees C was significantly reduced compared with IMC-3 cells. At 40 degrees C, however, hyperthermia increased platinum accumulation by factors of 1.4 and 1.8 in IMC-3 and IMC-3-DDP cells, respectively. These findings indicated that CDDP sensitivity was hyperthermically chemopotentiated in CDDP-resistant variants rather than in the control clones. Thus, clinical cancer chemotherapy with CDDP may be improved by an appropriate combination with hyperthermia even at 40 degrees C.
Ohtsubo
T
T
Department of Otolaryngology, Fukui Medical School, 23 Shimo-aitsuki, Matsuoka, Fukui 910-11, Japan.
Saito
H
H
Tanaka
N
N
Matsumoto
H
H
Sugimoto
C
C
Saito
T
T
Hayashi
S
S
Kano
E
E
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002277:Carcinoma / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D006979:Hyperthermia, Induced; D008441:Maxillary Neoplasms / Q000473:pathology; D010984:Platinum / Q000378:metabolism
D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin