Effect Of Endogenous Cannabinoid System On Breast Cancer Invasion And Metastasis Under Chronic Intermittent Hypoxia

Objective:To explore the effect of chronic intermittent hypoxia on the occurrence and metastasis of breast cancer by establishing a chronic intermittent hypoxic mouse model of breast cancer.To provide a basis for further effective intervention in the pathological process between obstructive sleep apnea hypopnea syndrome(OSAHS)and breast cancer,And provide new ideas for the treatment of OSAHS patients with breast cancer..Methods:1.Mouse breast cancer model was established,and the mice were randomly divided into normal oxygen group(Control),chronic hypoxia group(CH)and chronic intermittent hypoxia group(CIH).The tumor size was measured,the number of lung metastasis nodules was counted,and the effect of chronic intermittent hypoxia on the proliferation and metastasis of breast cancer was observed,and detect the expression of cannabinoid receptors CB1 and CB2 in breast cancer tissues under chronic intermittent hypoxia;2.Recombinant plasmids sh-CB1,sh-CB2,sh-CB1/CB2,which interfere with the RNA(shRNA)fragment of CB1 and CB2,MCF-7 cells containing sh-CB1,sh-CB2,sh-CB1/CB2 recombinant plasmid were injected into mice to observe the effect of chronic intermittent hypoxia on proliferation and metastasis of breast cancer afterinterfering RNA.Results:1.Compared with the control group,the tumor volume of CH group and CIH group increased significantly with time,and the difference between CIH group and normoxia group was more significant.At the same time,the lung tumor nodules of mice exposed to CH and CIH were more.The lungs of the mice exposed to CIH had more nodules in the lungs,and HE staining was performed on the tumor sections.The data showed that the blood formation in the CH group and the CIH group increased,especially in the CIH group.2.Western blot analysis showed that the expression of CB1 and CB2 was up-regulated in CH and CIH,and the induction effect of CIH was higher than CH in mouse breast cancer tissues fed under chronic intermittent hypoxia.3.Under chronic intermittent hypoxic conditions,in the interfering CB1 group(sh-CB1),interfering CB2(sh-CB2)group and simultaneously interfering with CB1 and CB2(sh-CB1/)compared with the negative control group(sh-NC)CB2)group,We observed a sharp decline in tumor volume and a decrease in the number of tumor nodules in the lungs of mice,especially in the CB1 and CB2(sh-CB1/CB2)groups,and the reduction in tumor volume was more pronounced.Conclusion:1.Chronic intermittent hypoxia(CIH)can cause proliferation of mouse breastcancer;2.Chronic intermittent hypoxia(CIH)can lead to the metastasis of mouse breastcancer;3.ECS may be involved in the formation of mouse breast cancer caused by CIH;4.Blocking ECS may have an inhibitory effect on the development of CIH-induced mouse breast cancer.