| ObjectiveIt is an usefull treatment by giving aromatase inhibitor, which is the first choice for patients after menopause, in endocrine therapy of breast cancer. Though it could control the recurrence and metastasis of breast cancer, it could reduce the leveal of E2, which could result in loss of calcium in bone and osteoporosis. It is undoubt that the patient, who is given aromatase inhibitor in breast cancer treatment, will experience fracture、pain of muscle and joint which could decrease the quanlity of life on patien. It is necessary to treat these diseases. It is an advantage to treat these diseases by Traditional Chinese Medical treatment which enphase on the concept of the whole and dialectical treatment. This study imitate the clinical fact that patien suffering breast cancer is given aromatase inhibitor for endocrine therapy after operation. The mice with ovariectomy were given anastrozole and prescription of bushen jianpi after cutting off breast cancer. Then the effectiveness of this recipe was evaluated in treatment of osteoporosis involved in endocrine therapy, and exploration of mechanism of bone loss. At the same time, the effectiveness of this recipe was evaluated in adjuvant treatment of breast cancer, and exploration of this mechanism.MethodsEtablishment of castrated model by ovariectomizing in BALB/c mice, and murine breast cancer cell line 4T1 was injected into right armpits in mice after 8 weeks. Cutting out of tumor, which was more than 0.3 cm in diameter on the surface, after 3 weeks. Pathological analysis was conducted in the cut tumor tissues. mice, without tumor recurring after one week of operation, were divided to groups. While pharmaceutical were given to them for 4 weeks:20ml/kg BW/d of normal saline were given to the sham operation group and the blank group; 0.15mg/kg BW/d of anastrozole were given to the control group; 0.15mg/kg BW/d of anastrozole and 1.5mg/kg BW/d of alendronate were given to the alendronate group; 0.15mg/kg BW/d of anastrozole and 33.5g/kg BW/d of prescription of bushen jianpi were given to the bushen jianpi group.0.15mg/kg BW/d of anastrozole,1.5mg/kg BW/d of alendronate and 33.5g/kg BW/d of prescription of bushen jianpi were given to the combined group. After 24h from the last giving pharmaceutical, blood were collected from eyepit, centrifugal separation, and the serum were collected for analysis of levels of estradiol (E2) and alkaline phosphatase (ALP). After collecting blood, mice were executed, tumor recurring in inject point were cut for weight and pathological analysis. Femur and tibia of both sides were extracted, without muscle and softer tissues, for bone mineral density (BMD) measurement of left femur and detection of levels of bone calcium and phosphorus via right femur and tibia.Results1. The levels of E2 in the sham operation group、the blank group、the control group、the alendronate group、the bushen jianpi decoction group and the combined group were 58.98±7.89 pg/ml、25.43±5.36 pg/ml、12.83±3.05 pg/ml、11.52 ±1.99 pg/ml、12.93±2.65 pg/ml、13.35±3.06 pg/ml, respectively. For these results, it could make summaries that the establishment of castrated model was success, with reduction of E2 by giving aromatase inhibitor, and that the levels of E2 was unaffected by different treatment after castrating.2. The levels of BMD in the sham operation group、the blank group、the control group、the alendronate group、the bushen jianpi decoction group and the combined group were 0.239±0.038 mg/cm2、0.203±0.018 mg/cm2、0.201±0.010 mg/cm2、0.234±0.010 mg/cm2、0.207±0.009 mg/cm2、0.237±0.007mg/cm2, respectively. The levels of ALP were 4.86±1.01 ng/ml、6.23±0.67 ng/ml、 6.57±0.61 ng/ml、5.09±0.39 ng/ml、6.01±0.12 ng/ml、4.96±0.10 ng/ml, respectively. The quantity of calcium in the bones were 61.6±6.0 mg/g、52.51 ±5.62 mg/g、51.43±6.92 mg/g、58.87±6.00 mg/g、52.19±5.14 mg/g、59.23± 3.83 mg/g, respectively.The quantity of phosphoru in the bones were 30.46 ±3.45 mg/g、25.31±3.13 mg/g、24.03±3.63 mg/g、28.45±4.53 mg/g、25.02 ±3.33 mg/g、28.63±6.27 mg/g, respectively. For these results, it could make summaries that the bushen jianpi decoction can significantly reduce the level of ALP, relieving the trend of bone loss, but without significant reduction of bone loss, and that the bushen jianpi decoction combined with alendronate can significantly improve the levels of BMD、bone calcium、bone phosphorus in mice experiencing endocrine therapy, with treatment of osteoporosis.3. The dormancy rates of the sham operation group group、the blank group、 the control group、the alendronate group、the bushen jianpi group and the combination group were 0%、20%、10%、20%、50%、60%, respectively. The tumor inhibition rates of the control group、the alendronate group、the combination group、the bushen jianpi group were -13.58%、 0%、45.68%、54.32%, respectively. The tumor inhibition rate of groups with bushen jianpi decoction, the bushen jianpi group and the combination group, were higher than groups without bushen jianpi decoction, the control group and the alendronate group. The tumor inhibition rate of the combination group was higher than the bushen jianpi group, but without significant difference (P>0.05). As these result, it could make summarie that the combination of bushen jianpi decoction and alendronate could increase the inhibition ability of tumor recurrence.4. The immunohistochemical stainings of ER in tumors from every group were negative before treatment. After treatment, some recurrence tumors from groups with bushen jianpi decoction showed weakly positive in immunohistochemical stainings of ER, while recurrence tumors from groups without bushen jianpi decoction were the same. The immunohistochemical stainings of PR in tumors from every group were negative before treatment, and after treatment the same. As these result, it could make summarie that bushen jianpi decoction could increase express of ER in some exten, without influence on express of PR. ConclutionThe bushen jianpi decoction could adjuvant promote metabolism of bone in osteoporosis caused by endocrine therapy of breast cancer. The bushen jianpi decoction could increase express of ER, make breast cancer cell sensitive to the level of E2. Therefore, it could enhance the treatment of breast cancer by aromatase inhibitors. |
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