Objective    To explore the effect of different doses of cyclophosphamide (CTX) on the drug-resistance of implanted human A549 lung cancer in nude mice

and investigate the anti-tumor effect and toxicity.     Methods    BALB/c nude mice bearing A549 lung carcinoma were randomized into low-dose metronomic (LDM) CTX group

maximum tolerate dose (MTD) CTX group and normal saline group. The changes of tumor volume

weight and toxicity were observed. Expression of glutathione S-transferase-π (GST-π) and lung resistance-related protein (LRP) in the tumor were detected by immunohistochemistry SP method.     Results    In LDM CTX group

the tumor grew fast at first

then slowed down gradually and grew slowly for a long time

while in MTD CTX group tumor grew slowly at first

then it accelerated. Side effects of chemotherapy: the weight of nude mice was lost persistently in MTD CTX group

while lost insignificantly in LDM CTX group. No obvious toxicity was observed in LDM CTX group. GST-π and LRP expression in LDM CTX group were not significantly different from those in the control

but significance was seen in MTD CTX group compared with those in the control (P<0.05). GST-π and LRP expression in LDM CTX group were significantly different from those in the MTD CTX group (P<0.05).     Conclusion     The low-dose metronomic regimen of CTX can lead to less drug resistance and suppress the tumor growth more notably and persistently

and decrease toxicities and side effects compared with traditional maximum tolerated dose regimen.