| Lung cancer is the first major cancer,and there are about one lung cancer patient in every four cancer patients.In the late stage of lung cancer,bone metastasis is prone to occur,and bisphosphonates are generally used in clinical treatment.Although bisphosphonates reduce skeletal-related events(fracture,spinal cord compression,etc.),they do not prolong survival.There is an urgent need for new drugs that can effectively treat bone metastases from lung cancer.Through literature research,docetaxel and gambogic acid were combined to study the anti-lung cancer bone metastasis activity.The results are as follows:1.In vitro MTT assay for the anti-tumor activity of docetaxel and gambogic acid in combination with LLC on mouse Lewis lung cancer cells:48 h treatment,docetaxel(DTX)group,gambogic acid(GA)group,and multiple western The IC50 values for the combination of paclitaxel and gambogic acid were 0.049 ?M,0.073 ?M and 0.035 ?M,respectively(n=3,p<0.01).After treatment for 72 h,the IC50 values of the combination of docetaxel,gambogic acid,and docetaxel and gambogic acid were 0.029 ?M,0.051?M and 0.013 ?M(n=3,p<0.01),respectively.The experimental results showed that the combination of docetaxel and gambogic acid was superior to docetaxel or gambogic acid in the antitumor activity,and the drug efficacy was enhanced with time.2.The bone metastasis model of Lewis lung cancer in C57BL/6 mice was used as the model.The lung cancer bone metastasis model was divided into 4 groups:blank group,docetaxel group,gambogic acid group and docetaxel garcinic acid combined group.After injection,the dose of docetaxel was 10 mg/kg,the dose of gambogic acid was 4 mg/kg,and continuous administration was performed for 10 days.The overall survival time of the mice in the blank group was 19.27±1.32 days,and the overall survival time of the docetaxel group.At 25.75±0.67 days,the overall survival period was 23.99 ± 0.58 days in the gambogic acid group,32.61 ± 1.06 days in the combination of docetaxel and gambogic acid(n=10,p<0.01),and the docetaxel group or Compared with the gambogic acid group,the survival time of mice treated with docetaxel garcinic acid was significantly prolonged.3.The mean body weight of mice in the blank control group was 19.17±0.67g,the average body weight of mice in the docetaxel group was 17.26±0.58g,the average body weight of the mice in the gambogic acid group was 16.88 ±0.65g,docetaxel and gambogic acid The average weight of the combination group was 18.33 ±0.62g(n=10,p<0.01).The body weights of the docetaxel and gambogic acid groups were smaller than that of the combination group.The results showed that the combination of docetaxel and gambogic acid had the lowest toxicity..The tumor inhibition rate was calculated according to the tumor volume of mice,which was 60.35±2.79%in docetaxel group,62.17±2.53%in gambogic acid group,and 69,54±3.11%in combination of docetaxel and gambogic acid.The combination of paclitaxel and gambogic acid had a higher tumor inhibition rate than docetaxel and gambogic acid.The results showed that the combination of docetaxel and gambogic acid inhibited the tumor more strongly than docetaxel or gambogic acid..After the lung cancer bone metastasis model was established,the degree of bone destruction after the X-ray irradiation was observed in each group of mice.The tumor in the tumor of the leg of the mouse was inhomogeneous,the bone was hypertrophied and fractured,and the bone skin showed a tendency to extend to the tumor tissue.In the blank group,the bone destruction was the most serious.The docetaxel group and the gambogic acid group were slightly more severe.Compared with the docetaxel group or the gambogic acid group,the docetaxel-gambogic acid combination group had less bone destruction,and the results showed that the combination drug was exerted.A larger bone metastasis has anti-tumor effects.6.By observing the pathological section of bone tissue,the outer epithelium of osteoblasts in the blank group,docetaxel group,and gambogic acid group disappeared,osteoporotic tissue was formed,and cytoplasm atrophy in the trabecular bone,and the tumor cells were hypertrophied.Irregularities spread throughout the bone marrow cavity,irregularly arranged.Bone destruction was most serious in the blank group;the docetaxel group and the gambogic acid group were slightly more severe,and compared with the docetaxel group and gambogic acid group,clear bone epidermis and cytoplasm were observed in the docetaxel joint glycyrrhizic acid group.Bone destruction is lighter.The results show that the combination group is a more effective inhibitor of bone metastasis in lung cancer.In vitro and in vivo experiments confirmed that docetaxel and gambogic acid combined with anti-lung cancer bone metastasis activity,further through the migration of Lewis lung cancer cells and induced macrophage RAW264.7 mouse osteoclast formation experiments The mechanism of anti-cancer bone metastasis in combination with taxol and gambogic acid was studied as follows:1.The migration of LLC cells in mouse Lewis lung cancer cells was as follows:compared with the blank control group,the cell migration inhibition rate was 52.83 ±3.44%in the docetaxel group,46.22±4.17%in the gambogic acid group,and docetaxel.The inhibition of cell migration was 64.77±3.75%(n=3,p<0.01)in combination with gambogic acid.The results showed that docetaxel combined with gambogic acid could inhibit the migration of LLC cells in Lewis lung cancer cells in mice,and the inhibitory effect was stronger than docetaxel group or gambogic acid group.2.Mouse Lewis lung cancer cell LLC and mouse macrophage RAW264.7,after TRAP staining,compared with the blank control group,the osteoclast formation rate in the docetaxel group was 73.43%± 2.97%,gambogic acid group The osteoclast formation rate was 86.12%±2.34%.The osteoclast formation rate in the combined docetaxel and gambogic acid group was 63.12 ± 2.75%.The results showed that osteoclast formation was formed in the combination of docetaxel and gambogic acid group.The lowest rate can inhibit mouse Lewis lung cancer cells LLC-induced macrophages RAW264.7 mouse osteoclast formation.Due to the poor water solubility of docetaxel and gambogic acid,a toxic co-solvent is needed for intravenous administration.In this paper,water-soluble albumin-wrapped docetaxel and gambogic acid nanoparticles(DTX-GA-)were prepared by high-pressure homogenization emulsification.BSA-NPs)and bone metastasis activity of Lewis lung carcinoma in C57BL/6 mouse model were studied.The results of the study were as follows:1.Preparation of DTX-GA-BSA-NPs,according to docetaxel standard curve and gambogic acid standard curve,the entrapment efficiency of DTX-GA-BSA-NPs was 86.3 ±2.4%,drug loading was 8.7± 1.2%The particle size is 102.0± 18.64 nm.The average survival time of mice treated with DTX-GA-BSA-NPs in bone metastasis model of mice with lung cancer was 31.58 ± 1.87d,and the average survival time of docetaxel joint combined group was 32.61 ±1.06d.The average body weight of the docetaxel and gambogic acid group was 18.33 ±0.62 g,the average body weight of the DTX-GA-BSA-NPs group was 18.86 ±0.88 g,and the body weight of the docetaxel joint group was less than that of the DTX-GA-In the BSA-NPs group,the difference was statistically significant(n=10,p<0.01).The experimental results showed that the side effects of DTX-GA-BSA-NPs on mice were smaller than those of the combined group.DTX-GA-BSA-NPs had a significant effect on the survival of lung cancer bone metastasis model.Summary:The Jin's formula is calculated as q=1.17,(q?1.15 when the two drugs have a synergistic effect),the results show that docetaxel and gambogic acid in combination for the treatment of lung cancer bone metastasis have a synergistic effect,and anti-cancer The activity was higher than docetaxel and gambogic acid alone. |
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