Antitumor effect of thermosensitive CDDP-liposomes on human osteosarcoma cells in culture.
We have administered cis-diamminedichloroplatinum (II) (CDDP) containing thermosensitive liposome and simultaneous hyperthermia into human osteosarcoma cells (OST) and studied the antitumor effects. Experiments were conducted under the following three different culture conditions as follows, (1) drug treatment alone, (2) hyperthermia after drug treatment, and (3) simultaneous hyperthermia and drug treatment. Antitumor effects were estimated by inhibition of DNA synthesis and decrease in cell growth rates. The antitumor action of simultaneous hyperthermia and drug treatments was the most dominant and synergistic among three experimental conditions. Accumulation of cellular platinum from thermosensitive CDDP-liposomes was markedly enhanced by hyperthermia. Flow cytometric analysis of the cell cycle indicated that CDDP-liposomes only under the simultaneous application of hyperthermia released free CDDP, and evoked cell accumulation in S and G 2/M phase. The results suggested that thermosensitive CDDP-liposomes were not taken up into cells by endocytosis, and released free CDDP into culture media under hyperthermia at 42 degrees C. From these, we have concluded that administration of thermosensitive CDDP-liposomes and simultaneous local hyperthermia could be a promising method for the treatment of osteosarcoma especially in the extremities.
Hattori
M
M
Department of Orthopaedic Surgery, Nagoya City University Medical School, Aichi, Japan.
Matsui
N
N
Ohta
H
H
Otsuka
T
T
Yamada
K
K
Asai
K
K
Kato
T
T
D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D006979:Hyperthermia, Induced; D008081:Liposomes; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004337:Drug Carriers; D008081:Liposomes; D002945:Cisplatin