抄録
Calmodulin is an ubiquitous Ca2+-binding protein which regulates a number of Ca2+-dependent functions. The cell calmodulin content increases after the synthetic phase and reaches the maximum level at G2 and early mitotic phases. Moreover, malignant transformation was found to represent a general mechanism that results in a specific increase in the intracellular content of calmodulin. When the calmodulin content in the tumor cells can be altered by administration of a calmodulin antagonist, growth of the transplanted glioma may be regulated. In this paper, the antitumor effect of calmodulin angatonist W-7 was examined in a rat glioma transplant model.
1) The control of intraperitoneally transplanted rats had a mean survival of 16.7±1.6 days after transplantation. W-7 1.0 mg/kg intraperitoneal injection for 10 days showed 37.8% increased life span (ILS) (P<0.01). W-7 3.0 mg/kg also showed 15.0% ILS (P<0.05). 2) The control of intracerebrally transplanted rats had a mean survival of 19.4±2.2 days after transplantation. No increase in the life span was observed in intracerebrally transplanted rats compared to the control at a dosage of W-7 1.0 mg/kg or 3.0 mg/kg intraperitoneal injection for 10 days. 3) Local application of W-7 1.0 mg/kg into the transplanted tumor in the cerebrum for 10 days showed 12.4% ILS (P<0.01), and 18.0% ILS (P<0.05) was obtained at the dosage of 3.0 mg/kg local application for 10 days. From these results, it is expected that direct injection of a calmodulin antagonist W-7 into the tumor is effective for the treatment of glioma.
