Growth control of C6 glioma in vivo by nerve growth factor

Treatment with nerve growth factor (NGF) causes differentiation of rat C6 glioma cells and strongly inhibits their proliferation in vitro. This suggests that induction of NGF-mediated differentiation may provide a novel therapeutic approach to growth control of glial tumors. We examined the effects of NGF treatment on the growth potential of C6 glioma, which expressed NGF receptor in vivo. C6 glioma cells (1 x 10(6) cells/10 microl) were transplanted into the rat striatum. After 4 days, the animals were given successive injections of 100 ng NGF into the growing tumor at every 4 days (n = 10 rats). Controls were subjected to identical procedures with vehicle which did not contain NGF (n = 10 rats). At 14 days after transplantation, we evaluated the tumor volume, proliferative cell index (PCI) based on the MIB-1 immunoreactivity and enzyme activities related to energy metabolism by enzyme histochemistry. We found that the NGF treatment markedly reduced the tumor volume of the C6 glioma (34.00 +/- 8.47 mm3 to 7.22 +/- 4.92 mm3, p < 0.01). NGF treatment also decreased the PCI (33.34 +/- 9.57% to 3.85 +/- 3.56%, p < 0.01) with a negative correlation with tumor volume (r = 0.972, p < 0.01), and the hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6PDH) activities (p < 0.01 and p < 0.01, respectively) which reflect the demand for nucleic acid synthesis for proliferation through the glycolytic and pentose phosphate pathways. The present results demonstrate for the first time that inhibition of tumor cell proliferation of C6 glioma by NGF occurs in vivo, probably through the NGF-mediated differentiation of C6 glioma cells which has been observed in in vitro studies.