The Effect of Ginkgo Biloba Extract on the Fractionated Radiation Therapy in C3H Mouse Fibrosarcoma

Kim, Jong Hoon; Ha, Sung Whan; Park, Charn Il

Abstract

PURPOSE: A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle.
MATERIALS AND METHODS
Fibrosarcoma (FSaII) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment.
RESULTS
When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD (days)=0.26X D (Gy)+.13 in the radiation alone group, and the TGD (days)=0.30X D (Gy)+.13 in the radiation with GBE group. As a result, the enhancement ratio was 1.19 (95% confidence interval; 1.13~1.27). Laser Doppler flowmetry was used to measure the blood flow. The mean blood flow was higher in the muscle (7.78 mL/100 g/min in tumor and the 10.15 mL/100 g/min in muscle, p=0.0001) and the low blood flow fraction (less than 2 mL/100 g/min) was higher in the tumor (0.5% vs. 5.2%, p=0.005). The blood flow was not changed with the GBE in normal muscle, but was increased by 23.5% ( p=0.0004) in the tumor.
CONCLUSION
Based on these results, it can be concluded that the GBE enhanced the radiation effect significantly when used with fractionated radiotherapy as well as with single fraction irradiation. Furthermore, the GBE increased the blood flow of the tumor selectively.