Application of Ginkgo biloba L. extract at early stage of tumor development helps cyclophosphamide inhibit the growth of tumor cells

Abstract Background: There is inconsistency in the application of antioxidants in tumor treatment. This study explored whether the application of an antioxidant at the early stage of tumor transplantation enhances efficacy of a chemotherapeutic agent in inhibiting tumor cell growth. Methods: EMT-6 cells were injected into 48 ICR mice. 24h later, cyclophosphamide (CTX) and Ginkgo biloba L. extract (GBE) were administered to mice separately and in combination. Apoptotic markers and related signaling pathways were measured. Tumor weights were compared and survival analysis was used to investigate latency periods in the three treatment groups compared to a PBS control group. Results: The mice administered GBE and CTX had significantly lower tumor weights compared with those administered PBS (p=0.01), however, the mice administered CTX did not have significantly lower tumor weight compared with those administered PBS (p=0.19). The expression of NF-κB, IκB-ɑ,, and the phosphorylation of NF-κB, IκB-ɑ, were all significantly decreased in the tumors from GBE+CTX (p<0.05). Moreover, the ratio of Bax/Bcl-2 was significantly higher for the tumors of mice administered GBE+CTX than that of mice administered GBE, CTX, or PBS (p<0.05), the expression of FADD, Caspase-8, and Cyto-C was significantly increased in the tumors of mice administered GBE+CTX compared with those administered PBS or GBE (p<0.05). Conclusions: Application of an antioxidant at an early stage of tumor transplantation could help chemotherapeutic agents inhibit the growth of tumor cells. GBE+CTX treated mice showed a longer latency period to tumor development and markers that consistently indicated greater apoptotic activity and reduced tumor promotion.