Enhancing effect of chemotherapy and reducing toxicity of 20(S)-protopanaxadiol on tumor-bearing nude mice

Objective To observe the enhancing effect and reducing toxicity of 20(S)-protopanaxadiol (PPD) in combination with cyclophosphamide (CTX) on transplanated tumor human lung carcinoma A549 cells.Methods The transplanted tumor models with human lung carcinoma A549 cells were established and then divided randomly into six groups: control group,PPD group,low dose CTX group,high dose CTX group,PPD combined with low dose CTX group and PPD combined with high dose CTX group.The mice in each group were injected intraperitoneally with same amount of CMC,PPD (50 mg·kg-1·d-1),CTX (10 mg·kg-1·d-1),CTX (20 mg·kg-1·d-1),CTX(10 mg·kg-1·d-1)+PPD (50 mg·kg-1·d-1) and PPD (50 mg·kg-1·d-1)+ CTX (20 mg·kg-1·d-1),respectively.After administration for 15 d,the mice were killed and the mouse weight,tumor weight and volume,the number of WBC in peripheral blood, the count of bone marrow nucleated cells,spleen and thymus indexes,proliferation of T lymphocytes and nature killer cell activity were detected.At the same time,the apoptotic rate and activity of caspase-3 were analyzed by flow cytometry.Results Compared with CTX groups,the inhibitory rate of tumor in PPD(50 mg·kg-1) +CTX group increased (P0.01),the count of bone marrow nucleated cells increased (P0.01),the spleen and thymus indexes increased (P0.01), the proliferation ability of T lymphocytes (P0.05)and nature killer cell activity increased (P0.01). Compared with CTX groups,the apoptotic rates(P0.01) and activities of caspase-3 in PPD+CTX groups increased significantly(P0.05),but there was no significant difference between PPD and CTX groups.Conclusion PPD could significantly enhance the anti-tumor activity of CTX against lung cancer on nude mice and reduce the side effects simultaneously by up-regulating the activity of caspase-3 and inducing the apoptosis.