The Study Of Inhibition Of Sunitinib To Advanced Breast Cancer Model

Objective:This study is to explor if sunitinib can instead traditional chemotherapy or if it combined with traditional chemotherapy can improve curative effect by establishing an advanced breast cancer model. And then provide a theoretical basis for the targeted drug in clinical application by observing the inhibition of the targeted drug alone, combined with traditional chemotherapy compared to traditional chemotherapy on the model.Method: Establishing mice advanced breast cancer model bearing 4T1 breast cancer cells, which were randomly divided into 4 groups, called the control group (C), sunitinib group (S), docetaxel group ( D) and sunitinib combined with docetaxel group (S+D). The mice bearing 4T1 breast cancer cells were killed at the end of the experiment. Before they were killed, body weight of mice were measureed for statistics comparison. The implantation tumors of the mice signed with EGF fluorescent probe injected to the mice caudal vein were imaged by Pearl imager imaging system to compare the fluorescent density value. The implantation tumors and all lungs were removed out to compare the size of implantation tumors in each group and the number of lung metastases. And then the implantation tumors were made into single cell suspension, were analyzed of apoptosis, cell cycle and proliferation index(PI) by flow cytometry, then compared each groups of tumor apoptosis and proliferation index (PI).Results:1 After injecting 4T1 breast cancer cells , all mice developed the tumors, mice advanced breast cancer model bearing 4T1 breast cancer cells was successfully established.2 Group C mice body weight was 18.14±1.25g, group S 17.50±2.02 g, group D 15.90±2.10g,group S + D 17.38±2.15g. All drug intervention groups mice body weight were lighter than those in group C, but only the group D and group C were significantly different (P < 0.05). Although the group D mice body weight were lighter than those in group S and S + D, no significant difference was found between the two groups (P > 0.05).3 The implantation tumor volume of group C mice was 3191.46±517.90mm3, group S 2518.35±263.46 mm3, group S + D 1984.42±206.47mm3, group D 1999.46±278.57mm3. All drug intervention groups mice tumor volume were smaller than the group C, the difference was statistically significant (all P < 0.05); group S + D and group D mice tumor volume were smaller than those in group S , and the difference was statistically significant (all P < 0.05), group S + D tumor volume was smaller than those in group D, but the difference was not found statistically significant (P > 0.05).4 The implantation tumors of the mice were imaged by Pearl imager imaging system when EGF fluorescent probe was injected to mice caudal vein to sign the tumor, and then compared 4 groups of implantation tumor fluorescence intensity values, the results were as follow: the implantation tumor fluorescence intensity value of group C was 8.58±0.61E3,group S 6.30±0.29 E3, groupS+D3.07±0.36E3, groupD3.14±0.60E3.The implantation tumor fluorescence intensity value of all drug intervention groups were lower than the group C, the difference was statistically significant (all P < 0.05); group S + D and group D were lower than those in group S, and the difference was statistically significant (all P < 0.05), group S + D was lower than those in group D, but the difference was not found statistically significant (P > 0.05).5 The number of lung metastases were count by the stereo microscope: the lungs of 4 group mice were all found metastatic by stereo microscope. The median number of group C were 48, group S 31.5, group D 14, group S+D7.5, by statistical comparison, group S was no significant difference compared to group C, group D and group S + D compaired to group S and group C were significantly different (all P < 0.05).6 Implantation tumor cell apoptosis rate and cell cycle were analyzed by flow cytometry, proliferation index( PI )was computed based on cell cycle . The results were as follow: 4 groups of mice were of different levels of implantation tumor cell apoptosis: C group 39.19±16.91%, D group 39.17±13.01%, S + D group 46.79±11.30%, S group 36.37±1.57%, but no significant difference among the groups(P > 0.05). Implantation tumor cell PI for 4 groups of mice were not the same: group C 46.49±10.77%, group S 38.49±6.90%, group S + D 42.57±5.34%, group D 41.26±8.06 %, no significant difference among the groups either(P > 0.05).7 All the tumors and lungs specimens were paraffin-embedded and HE stained, the tumors were confirmed invasive breast cancer and lung node proved to be metastatic by microscopy.Conclusions:1 It is successfully established mice advanced breast cancer model bearing 4T1 breast cancer cells, and can carry out study further;2 Sunitinib has some anti-tumor effect in the mice model with advanced metastatic breast cancer,but the curative effect is poorer than traditional chemotherapy drug docetaxel;3 Sunitinib for advanced breast cancer is of a certain anti-tumor effect in primary tumor, but no significant inhibition of metastasis;4 Sunitinib combined with docetaxel has not yet increased side effects, but fails to improve efficacy;5 Sunitinib alone, or combined with traditional chemotherapy in the mice model with advanced metastatic breast cancer compared to traditional chemotherapy has no obvious advantage;6 Sunitinib is not recommended in treating advanced breast cancer.