Hattori M, Matsui N, Ohta H, Otsuka T, Yamada K, Asai K, Kato T
Department of Orthopaedic Surgery, Nagoya City University Medical School, Aichi, Japan.
Nihon Seikeigeka Gakkai Zasshi. 1992 May;66(5):476-84.
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.
我们将含顺二氯二氨铂（II）（CDDP）的热敏脂质体与同步热疗应用于人类骨肉瘤细胞（OST），并研究了其抗肿瘤作用。实验在以下三种不同培养条件下进行：（1）单独药物治疗；（2）药物治疗后热疗；（3）同步热疗与药物治疗。通过抑制DNA合成和降低细胞生长速率来评估抗肿瘤效果。在三种实验条件中，同步热疗与药物治疗的抗肿瘤作用最为显著且具有协同性。热疗显著增强了热敏CDDP脂质体中细胞铂的积累。细胞周期的流式细胞术分析表明，仅在同步热疗时，CDDP脂质体释放游离CDDP，并导致细胞在S期和G2/M期积累。结果表明，热敏CDDP脂质体不是通过内吞作用进入细胞，而是在42℃热疗条件下将游离CDDP释放到培养基中。由此我们得出结论，给予热敏CDDP脂质体并同步进行局部热疗可能是一种治疗骨肉瘤尤其是四肢骨肉瘤的有前景的方法。
