| Objective:To investigate the antitumor effects of combined adriarnycin and photodynamic therapy (PDT) on mice breast cancer model and explore its mechanism initially,in order to provide basal confirm for clinical application on breast cancer.Methods:24 BALB/c mice model with 4T1 mammary carcinoma was established and randomized into four groups when the tumors grew to 0.6-0.9cm:A, control group(without any treatment); B, PDT group(1mg/kg BPDMA+690nm laser irradiation); C, chemotherapy group(5mg/kg ADM); D, combined treatment group(1mg/kg BPDMA+690nm laser irradiation+5mg/kg ADM). On day 21 after treatment,6 mice of each group were sacrificed with their tumors removed and weighed to botain tumor weight. Flow cytometry was performed to analyze the apoptosis of breast cancer cells and microvessel density (MVD) immunohistochemical staining was carried out and the expressions of bcl-2 and bax proteins were detected by western-blot to explore the mechanism.28 BALB/c mice model was randomized into the same groups and the average survival time of each groups were observed with other mice.All experimental mice were weighed and tumor diameters were measured with vernier calipers before treatment and every two days after treatment.Results:1. Tumor volume(cm3):On day 21 after treatment,the tumor volumes of chemothrapy group and combination group are significantly smaller than those of control group (P<0.05). Compared with other groups,the tumor volumes of combination group decreased obviously (P<0.05).There is no significant difference of tumor volumes between control group and PDT group (P>0.05)2. Tumor weight(g) an TGI:Tumor weithts of mice in the combination group (0.83±0.12) was significantly lower than those in the control group (1.87±0.11) PDT group (1.25±0.19) and chemotherapy group (1.08±0.12) (P<0.05).TGI (55.61%) was higher in the combined treatment group than PDT group (33.16%) and chemotherapy group (42.25%) 3. Effect on the weights of animals:The chemotherapy group and the combined group had a loss of weight during the experiments, but the weight in the three experimental groups was not significantly different from that in the control group after treatment. (P>0.05)4. The average survival time of each groups as follows:A,44±0.83 days; B,46±0.68 days; C,52±0.98 days; D,59±1.87 days (P<0.05)5. The analysis of apoptosis with flow cytometry presentated that cell apoptosis was more obviously in the PDT group and the combined group. However, compared with other treatment groups,the combined treatment group had significantly higher fraction of apoptotic cells. (P<0.05)6. As to MVD, there is no statistical difference between control group (25.62±1.52) and chemotherapy group(24.52±1.56) (P>0.05).However, the PDT group (16.28±2.18) and the combined treatment group (11.79±1.83) had statistical difference (P<0.05)7. The western blots results demonstrated that the expression of bcl-2 protein obviously decreased, while the expression of bax protein increased and the value of bax/bcl-2 up-regulated in the combined treatment group.Conclusions:1. The combined treatment group had significantly anti-tumor effects and longer the survival of mice model; The PDT also had anti-tumor effect. However, the time of anti-tumor was short and had no effectiveness in the survival of mice model.2. The PDT group had lowest toxicity. Although the chemotherapy group and the combined treatment group had some toxicity and anti-tumor effect, no treatment related deaths occurred.3. Antiangiogenesis and inducing apoptosis of cancer cells are the main mechanism of anti-tumor effect, especially in the combined treatment group. |
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