LOCAL-ADMINISTRATION OF 7-BETA-HYDROXYCHOLESTERYL-3-OLEATE INHIBITS GROWTH OF EXPERIMENTAL RAT C6 GLIOBLASTOMA

The effect of 7 beta-hydroxycholesteryl-3-oleate on rat brain C6 gliob lastoma cells was studied. Three days after the inoculation of 2 x 10( 5) C6 cells into the frontal cortex of 6-day-old Wistar rats, two type s of liposomes [consisting of either phosphatidylcholine and monosialo ganglioside PG:GM1, 10:1 mol/mol) only, or containing 7 beta-hydroxych olesterol, 7 beta hydroxycholesteryl-3-oleate, 7 alpha-hydroxycholeste ryl-3-oleate, or 7-keto-cholesteryl-3-oleate] were injected into the x enograft. Ten days later, the animals were sacrificed, the tumors were stained with cresyl violet or hematoxylin/eosin, their volumes determ ined by image analysis, and their development followed by magnetic res onance imaging. The mean (+/- SE) tumor volume was 4.4 +/- 1.0 mm(3). The injection of liposomes without oxysterol had no effect on tumor gr owth, whereas injection of liposomes containing 7 beta-hydroxycholeste ryl-3-oleate (36 nmol) gave rise to a marked decrease in tumor volume (from 4.4 +/- 1.0 to 0.7 +/- 0.4 mm(3)). Seven nmol had no effect on t umor growth, 72 nmol were as efficient as 36 nmol, and 144 nmol attenu ated the tumor volume by 50% only. Liposomes containing 72 nmol of ole ic acid enhanced the tumor volume 4-fold. These findings were confirme d by magnetic resonance imaging. Thus, following induction of tumors i n both the right and left sides of the cortex and treatment of the rig ht side, magnetic resonance imaging indicated a significant decrease i n tumor volume on the right side only. When C6 cells and 7 beta-hydrox ycholeteryl-3-oleate were simultaneously injected, tumors did not deve lop in 80% of the animals. The clearance of [(3)h]7 beta-hydroxycholes teryl-3-oleate, of which 75% was converted to cholesterol, reached 99% after 48 h. Other oxysterols did not affect the tumor volume except t hat 7-keto-cholesteryl-3-oleate decreased the tumor volume by 50%. Thu s, the 3-fatty acyl ester and 7 beta-hydroxyl groups are apparently re quired for the antitumor growth effect. Taken together, these data sug gest that 7 beta-hydroxycholesteryl-3-oleate might be useful for local glioblastoma chemotherapy.