Inhibition Of Conventional Chemotherapy Combined With Metronomic Chemotherapy On Breast Cancer Xenografts In Nude Mice

Objective: To compare the antitumor effects in nude mice with human breast cancer with cyclophosphamide different chemotherapy regimens and to observe two balances: between pro-angiogenesis and anti-angiogenesis and between tumor cell proliferation and apoptosis.Methods:1.To establish breast orthotopic transplantation tumor model.2.20 nude mice bearing carcinoma were divided into 4 groups randomly: metronomic chemotherapy group(LDM),conventional chemotherapy group(MTD),combined group(LDM+MTD) and control group.3.Observe the general condition of mice and weight them every other day, at the same time measure the volume of subcutaneous tumor. WBC was counted every week. In the end, tumors were taken off and weighted to calculate inhibitory rates of each group.4.Immunohistochemistry was used to detect the expressions of MVD,VEGF,TSP-1 and PCNA.TUNEL was used to detect the apoptosis of the tumor cells.Results:1.All nude mice were in good condition throughout the trial period without significant side effects.2.Three chemotherapy regimens can inhibit the growth of xenografts in different degrees, whose inhibitory rates were 32.95%,41.75% and 69.15%,respectively.LDM and MTD had similar tumor growth curve. While the xenografts in combination group appeared to grow significantly slower than the other groups. 3. In the combination group and LDM group, xenografts expressed lower level VEGF and MVD and higher level TSP-1 than those in the other groups(p<0.05), but there is no significant difference between the two groups (p>0.05).4. There was lower expression of PCNA in the combination group and MTD group than its in the LDM and control group (p<0.05), but there is no statistically significant difference between the two groups (p>0.05). The apoptosis index (AI) in three chemotherapy groups had statically significant difference with control group (p<0.05). Furthermore, the AI in the combination group was highest.Conclusion: Conventional chemotherapy combined with metronomic chemotherapy has more powerful anti-cancer effects compared to the single conventional or metronomic chemotherapy without obvious side effect. The probable mechanism may be related with suppressing angiogenesis,inhibiting tumor cell proliferation and inducing apoptosis.