| Objective: To establish the breast cancer mice model and explore antitumor mechanisms of zoledronic acid.Material and methods : 32 female BALB/c mice were injected of 4TI breast cancer cells in the right breast pad. When the tumor volume was about 150-200mm3, the mice were randomly divided into four groups: control group, with 0.3ml normal sodium(NS)intraperitoneal injection , twice/week; zoledronic acid group,with zoledronic acid 5μg/mice subcutaneous injection,twice/week; docetaxel group , with docetaxel 15mg/kg intraperitoneal injection,twice/week; combination group: docetaxel intraperitoneal injection 15mg/kg, then zoledronic acid 5μg/mice subcutaneous injection, twice/week. After three weeks treatment, the tumor and metastases of mice model were showed by Pearl ImagerTM vivo imaging system. The apoptosis rates of tumor cells were detected by flow cytometry and mice lung metastases were counted with the stereo microscope. The remaining tumor and organs were fixed in 10% neutral formalin for pathological observation.All data was analyzed by SPSS13.0 for windows.Results:1 After injecting 4TI cells suspension, all mice achieved tumors on the 7th day. The average tumor volume in four groups have no statistical difference(P >0.05).2 Given different treatment, each group average volume of tumors grown in mice were as follows: control group 2814.91mm3, zoledronic acid group 2764.15mm3, docetaxel group 2106.81mm3, zoledronic acid and docetaxel combination group 1971.85 mm3. The combination group and docetaxel group compared with the control group were statistically significant, but there was no statistical significance between zoledronic acid group and the control. While the combined group volume was smaller than single drug group,there was statistical significance.3 Fluorescence imaging system showed the tumor same area and the fluorescent light density values order was: control group > zoledronic acid group > docetaxel group > the combination group. The average optical density value of the tumor area were: 6.57±0.25E3,6.25±0.43E3,3.07±0.36E3,2.07±0.28E3. The combination and docetaxel group compared with control group was statistically significant. While there was not statistical significance between zoledronic acid group and the control.4 After giving different treatment, the mice lung metastasis situation was as follows: control group 8/8, zoledronic acid group 8/8, docetaxel group 8/8, the combination group 6/8. Counting the lung metastasis of the mice: the control group 40.37, zoledronic acid group 36.12, docetaxel group 17.12, the combination group 7.37. The metastasis number was fewer in docetaxel group and combined group than the control group and zoledronic acid group, there was statistical significance. But there was no statistical significance between zoledronic acid group and the control.5 Flow cytology showed the combination group had a high cell apoptosis rate compare with the others, there was statistical significance.Conclusion:1 Apply 4TI cells suspension injection to establish mice breast cancer mode, has satisfactory controllability and relative property, has higher achievement ratio and the tumor can form much sooner.2 A single agent zoledronic acid doesn't demonstrate evident effect of inhibition of tumor growth and inducing apoptosis, reducing the role of lung metastasis, compared with the control group.3 A single agent docetaxel demonstrates the effect of inhibition of tumor growth, reducing the role of visceral metastasis compared with the control group, the inducion of tumor cells apoptosis not significant.4 Zoledronic acid and docetaxel combination group demonstrates more evident effect of inhibition of tumor growth and inducing apoptosis, reducing the role of visceral metastasis. Zoledronic acid has a synergistic effect of enhancing the role of docetaxel. |
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