| Objective:In this experiment,we established the MCF-7 breast cancer xenografts animal model of nude mice,to study the effects of the maximum tolerated dose (MTD) intermission combined with low-dose CTX metronomic chemotherapyon proliferation and angiogenesis,to observe the anti-tumor effect and the toxicityof mice,to investigate the feasibility of the conventional chemotherapy drugs in combination of different modes.Methods:1.Taking 20 female nude mice,injected the MCF-7 human breast cancer cells in the right breast of each mice,0.2ml,6×10~7/ml,estabilsh the animal model of tumor. 2.When the volume of tumor was about 150-200mm3,the mice were randomly divided into four groups and ecah group owns 5 mice.Group A: Low-dose CTX metronomic chemotherpy group (LDM):CTX 20mg/kd,once a day;Group B: Maximum tolerated dose CTX group (MTD):CTX 150mg/kg,was given3 times in the first week,every other day;Group C:Maximum tolerated dose combined with metronomic chemotherpy group (LDM+MTD):CTX 150 mg/kg,was given 3 times in the first week,every other day,then given CTX 20mg/kg,once a dy in the last 2 weeks.Group D: Control group(NS):equal volume of saline,once a day.They all received the intraperitoneal injection,21 days one cycle. 3.During the treatment, we obeserved the living conditions of nude mice every day,calculatethetumor size and the weight of nude mice every 2 days,counted the white blood cells in peripheral blood of nude mice every week. 4.When the 21days treatment was over,the mice were killed after 5 days observation,then dissected the transplanted tumor, measured the weight of it and calculate the inhibition rate of tumor;Detected the expression of Vascular endothelial growth factor (VEGF),microvess el density (MVD) and proliferating cell nuclear antigen (PCNA) of the tumor tissues by immunohistochemical SP method.Results:1.All treatment groups suppressed the growth of tumor.When the 14th daysof the treatment,the growth of tumor in group C was significantly slowly compared with each other groups,the tumor volume of each treatment group compared with the control group were statistically significant difference (P<0.05);the differences of tumor volume between each treatment group were no statistically significant (P>0.05) ;The differences of tumor volume was significantly:the volume of group C compared with the volume of group A and B was statistically significant (P<0.05);the differences between the tumor volume in treatment group compared with the control group was statistically significant (P<0.05);the difference of volume between group A and B was no statistically significant (P>0.05).2.Weights of tumor and the antitumor rates in each group were as follows:Group A: 0.755±0.257g,32.95%;Group B: 0.658±0.191g,41.57%;Group C: 0.390±0.033g,69.15%;Control Group: 1.126±0.241g.The tumor weights of treatment group were significantly lower than the control group,the differences were statistically significant (P<0.05); the tumor weights of Group C was significantly lower than Group A and B and the differences were statistically significant(P>0.05).3.At the end of the treatment,the 20 nude mice was all survived.The eatingof mice in control group was decling day by day,and the weight of mice was severe lossed.The mice in each treatment groups was in good general condition,andthere were no diarrhea,congestion and other phenomena.The weights observed:the weights of each treatment group compared with the control group was no statistically significant(P>0.05);the differents of mice weight between each treatment group were no statistically significant (P>0.05).Determination of white blood cells:the blood cells in each treatment group compared with the control group were nostatistically significant (P>0.05);the differences between each treatment group were no statistically significant (P>0.05).4.The level of VEGF and MVD in Group A and C was significantly lowe than Group B and control group,the differences were statistically significant (P<0.05); the level of VEGF and MVD in Group B was lower than the control group,the differences were no statistically significant (P>0.05).5.The level of PCNA in Group B and C was significantly lower than Grou p A and control group,the differences were statistically significant (P<0.05); the level of PCNA in Group A was lower than the control group,the differences wasno statistically significant (P>0.05).Conclusion:1.Low-dose CTX metronomic chemotherapy can reduce the level of VEGFand MVD,it inhibit the tumor growth by inhibiting the angiogenesis of tumor.2.The maximum tolerated dose of chemotherapy can reduce the level of PCNA,it inhibit the tumor growth by directly inhibiting the activity of tumor cells.3.Maximum tolerated dose intermission combined with low-dose CTX metronomic chemotherapy can inhibit the tumor cells proliferation and angiogenesis oftumor,the inhibition of tumor is better and do not increase toxicity,it is a feasibleand effective regimen. |
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