INVITRO RESPONSE OF HUMAN GLIOBLASTOMA AND CANINE GLIOMA-CELLS TO HYPERTHERMIA, RADIATION, AND CHEMOTHERAPY

Little is known about the sensitivity of human glioblastoma cells to hyperthermia alone and in combination with other therapies. We carried out in vitro cell survival studies on the human glioblastoma cell line U-87MG and our model canine glioma canine brain tumor (CBT) cells after multimodality treatment. Ionizing radiation was administered to flasks of cells in logarithmic growth at 500 rads (5 Gy) with consecutive treatment by hyperthermia, 1,3-bis-(2-cholorethyl)-1-nitrosourea (BCNU), or cisplatin. Cells were treated with single doses of BCNU at 5-mu-M with sequentially added radiation or hyperthermia and at 1 to 2-mu-g/ml of cisplatin with hyperthermia. Hyperthermia was administered in a precision controlled water bath at 44-degrees-C for 30 minutes in combination with chemotherapy or radiation. In general, the sensitivity of U-87MG and CBT cells was similar for all test regimens. For example, colony formation efficiency decreased by 64% in CBT cells and by 64.4% in U-87MG cells after hyperthermia alone at 44-degrees-C for 60 minutes. All combinations of BCNU, hyperthermia, and radiation administered in vitro produced enhanced cell killing, but the effects of multiple modalities were generally additive in both cell lines. When the effects of cisplatin and hyperthermia were studied, the combination produced additive cell killing in U-87MG cells and a synergistic killing response in CBT cells. We conclude that: 1) the sensitivity of human glioblastoma cells to heat is similar to that of other cancers; 2) that the in vitro sensitivity of the canine brain tumor to combinations of hyperthermia, ionizing radiation, and BCNU is similar to human glioblastoma and supports its use as an in vitro and in vivo test system; and 3) that hyperthermia is an effective potentiator of both ionizing radiation and chemotherapy for human and canine glioma cells.