HMA 세포내 산도증가가 온열과 항암화학 치료의 세포독성에 미치는 효과

Effect of Increased Intracellular pH by HMA on the Cytotoxicity of Combined Treatment of Hyperthermia and Chemotherapy

Purpose : The enhanced cytotoxic effect of combined treatment of hyperthermia and chemotherapy by increasing intracellular acidity with HMA was investigated. Materials and Methods : FSall tumor cells were injected on the hindlegs of female C₃H mice. When the tumor volume reached about 200mm³, experiments were performed on the groups classified as follows : Group Ⅰ : Control. Group Ⅱ : Melphalan alone (2.5mg/kg, 5mg/kg, 10mg/kg, 15mg/kg). Group Ⅲ : Heat alone (42.5°C for 1 hour). Group Ⅳ : Mephalan + Heat (42.5°C for 1 hour). Group Ⅴ : HMA(10mg/kg) + Melphalan(5.0mg/kg) + Heat(42.5°C for 1 hour). Each group included 8-12 mice on each experiment. HMA (3-amino-6-chloro-5-(1-homopiperidyl)-N-(diaminomethylene)-c-pyrazinecarboxamide). an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoide (DMS) and injected tnto the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of mephalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor volme reached at 1500mm³. Excision assay was performed on each group and repeated 2-4 times. Results : Tumor growth delay of each experimental group at 1500mm³ were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using FSall tumor cells, the mytotoxicity of each experimental groups was 1.2X10⁷, 1X10⁷, 6X10⁶, 1.7X10⁶ and 1X10⁵ clonogenic cells/gm respectively. When HMA was added to the combined treatment of heat and chemotherapy, the tumor growth was delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at 1500mm³ of tumor volume. conclusion : The combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.