To study the effects of external microwave hyperthermia on apoptosis and cell viability in three different cancer cell lines and in fibroblasts (as controls) and in a in vivo pleural metastasis animal model.
Mice were divided into three groups (8 mice/group): control group and two exposed group (mild, 39°C and moderate, 43°C). Orthotopic tumors are usually established on the lung or on the inner thoracic membrane 10-14 days after tumor inoculation. Mice were treated either by mild or moderate microwave hyperthermia on days 12, 13, 14, 19, 20, and day 21 after tumor inoculation. Seven days after the last treatment all mice were sacrificed.
| Exposure | Parameters |
|---|---|
|
Exposure 1:
2.45 GHz
Exposure duration:
three times (3 sec (37° C = control group), 4 sec (39° C) or 5 sec (43° C)) with a 2 sec interval; 3 days/week for 2 weeks
animal study
|
|
|
Exposure 2:
2.45 GHz
Exposure duration:
three times (3 sec (37° C = control group), 5 sec (39° C), 7 sec (43° C) or 9 sec (47° C)) with a 2 sec interval; 3 days/week
in vitro study
|
| Frequency | 2.45 GHz |
|---|---|
| Type | |
| Exposure duration | three times (3 sec (37° C = control group), 4 sec (39° C) or 5 sec (43° C)) with a 2 sec interval; 3 days/week for 2 weeks |
| Additional info | animal study |
| Frequency | 2.45 GHz |
|---|---|
| Type | |
| Exposure duration | three times (3 sec (37° C = control group), 5 sec (39° C), 7 sec (43° C) or 9 sec (47° C)) with a 2 sec interval; 3 days/week |
| Additional info | in vitro study |
| Exposure source |
|
|---|
The data revealed that cancer cells treated with moderate hyperthermia (43°C) showed significant apoptosis; the induction of apoptosis and the accumulation of sub G0 phase-G1 phase cells were dramatically increased in temperature dependent manner in the three cancer cell lines treated with microwave hyperthermia compared to untreated control cells. In contrast, no major effect was observed to normal fibroblast cells.
Western blot analysis indicated that the strong induction of apoptosis in hyperthermia exposed cancer cells is mediated both by the activation of caspase cascade and apoptotic regulation of Bcl-2 family.
The data of the in vivo investigation showed that metastasized tumors around the pleura and chest cavity were 75% reduced in size and weight after hyperthermia treatment compared to the control group. Harvested tumors demonstrated significant apoptosis in the moderate hyperthermia group. No significant adverse effects were observed including abnormal weight loss, skin burn, ulceration, and death.
The external microwave hyperthermia system may be possible alternative tool as a systemic hyperthermia therapy in severely advanced lung cancer patients. Further study is necessary to determine device safeness, efficacy, and synergistic effect to other possible combination therapies.
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