The Experimental And Clinica Studies Of Low-dose Cyclophosphamide Combined With Ginsenoside Rg3 On Advanced Non-small Cell Lung Cancer

Objective: To evaluate the efficacy of the combination of low - dose cyclophosphamide (CTX) and ginsenoside Rg3 for the antiangiogenic effect on lung carcinoma and to investigate its toxicity and efficacy in treating advanced non - small cell lung cancer patients. Method: C57/BL6 mice bearing lewis lung carcinoma were randomized into several groups , and received low- dose CTX , maximum tolerated dose(MTD) CTX , ginsenoside Rg3 and low- dose CTX combined with ginsenoside Rg3 therapy respectively. Then we monitored tumor growth, weight loss and survival of mice in each group. At the end of experiment, tumors were resected for immunohistochemical staining. Tumor microvascular density (MVD) ,Ki - 67 labeling index(Ki - 67 LI) , VEGF,Bcl - 2 and P53 gene expression were detected. Eligible patients had stage 111 /IV disease, adequate hematology and biochemistry, and had been treated previously with 4 cycles chemotherapy. They were randomized into two groups. The Therapeutic group was treated by CTX 50mg qd po plus ginsenoside Rg3 20mg bid po. The control group did not receive any treatment.Results: MVD,Ki - 67 LI and VEGF expression decreased in continous low - dose CTX therapeutic group. When ginsenoside Rg3 was added, those indicators were much lower, and Bel - 2 and P53 gene expressions were decreased either. During the experiment, we found that growth delays of tumor were more remarkable and enduring when low - dose CTX was used in combination with ginsenoside Rg3. The combination treatment was well tolerated, without apparent body weight loss, and showed the longest survival. Clinical study showed that: the serum VEGF is low and CD4+ , CD4+ /CD8+ cells is high in therapeutic group. The quality of life and survival of the patients were also raised in therapeutic group.Conclusion: These indicated that low - dose CTX combined with ginsenoside Rg3 inhibited angiogenesis of lung carcinoma more effectively, which resulted in decreased tumor proliferation and increased apoptosis. The continous low - dose regimen of CTX increases the efficacy of targeting the tumor microvasculature, and produces therapeutic activity with decreased toxicity. This experiment suggests a new safe therapeutic anticancer paradigm for controlling lung cancer, which will improve living quality of patient with cancer and prolong their survival.