Clinical Efficacy Of Warming Kidney And Dredging Collaterals For The Treatment Of Breast Cancer Bone Metastasis And The Effect Of OPG/RANKL Pathway

Objective:To summarize the clinical effect of Warming kidney and dredging collaterals on bone metastasis of kidney deficiency type breast cancer by clinical research,and to explore the effect of Warming kidn eyand dredging collaterals representative medicine on cinnamon Aconite on breast cancer cells and its influence on OPG/RANKL pathway in the co culture environment of breast cancer cells and osteoblasts,so as to explore the effect of Warming kidney and dredging collaterals ointment on bone metastasis of kidney deficiency type breast cancer objective to investigatethe clinical efficacy and mechanism of bone metastasis from breast cancer.Method:1.The patients with bone metastasis of breast cancer of kidney deficiency syndrome were randomly divided into control group and treat ment group.The control group was treated with zoledronic acid(ZOL);the treatment group was treated with Warming kidney and dredging collater als ointment on the basis of the control group.The course of treatment was 4 weeks,including 3 courses.2.Summarize and analyze the general situation、KPS、VAS、TCM syndrome quantitative score、serum calcium、CEA、CA125、CA15-3 before and after treatment,and detect the expression of RANKL,OPG and parathyr oid hormone by ELISA Except for the general situation of patients,the observation nodes of other items were before and after treatment,atotal of 2 times.3.Breast cancer cells(MDA-MB-231 cells)and osteoblasts(MC3T3-E1 cells)were cultured in vitro and divided into blank control group,cinnamon aconite drug pair group(drug pair group),ZOL group,cinna mon aconite plus ZOL group(combined group).4.CCK-8 method was used to detect the inhibition of MDA-MB-231 cells.The apoptosis of MDA-MB-231 cells was analyzed by flow cytometry.5.Construct the co culture system of breast cancer cells(MDA-MB-231 cells)and osteoblasts(MC3T3-E1 cells),namely MDA-MB-231/MC3T3-E1 co culture system and detect the effect of cinnamon aconite on OPG/RANKL pathway related cytokines by ELISA.Result:1.A total of 50 patients with bone metastasis of breast cancer with kidney deficiency syndrome were included in the study.During the treatment,3 patients in the control group and 1 patient in the treatment group could not be treated as planned and fell off.There were no significant differences in age,location and number of bone metastases,VAS,KPS and TCM syndrome quantitative score between the two groups(P>0.05).2.Before treatment,the VAS pain score of the control group was 3.36±1.09,and that of the treatment group was 3.23±0.97.After treatment the VAS score of the control group was 1.68±0.57,and that of the treatment group was 1.32±0.48.There was no difference between the two groups before treatment(P>0.05).After treatment the pain scores of the two groups were lower than those of the control group and the differences were statistically significant(P<0.05).3.In terms of functional status evaluation,the control group’s KPS increased from 75.91±8.54 to 89.09±2.94,while the treatment grou p’s increased from 76.25+2.82 to 89.17±2.82,the difference was nots tatistically significant(P>0.05).4.Before treatment,the TCM syndrome score of the control group was 5.91±1.51 and that of the treatment group was 6.45±1.86;after tre atment,the TCM syndrome score of the control group was 4.55±0.86 and that of the treatment group was 2.83±1.24;the total effective rate of the control group was 50.00%,and that of the treatment group was 79.16%,the differences were statistically significant(P<0.05).5.Before and after treatment,the serum calcium、CEA、CA125、CA15-3 of the control group and the treatment group had no significant changes within and between groups and the differences were not statistically significant(P>0.05).6.Before treatment,there was no significant difference in serum R ANKL,PTHrP and OPG between the groups(P>0.05);after treatment,there was no significant difference in serum RANKL between the groups(P>0.05);after treatment,serum PTHrP decreased and OPG increased in the group(P<0.05,P<0.001).After treatment,PTHrP in the treatmen tgroup was lower than that in the control group and OPG in the treatmen tgroup was lower than that in the control group The difference was stat istically significant(P<0.05).7.Compared with the blank control group,each group of drugs could inhibit the proliferation of MDA-MB-231 cells and the combined group had a stronger inhibitory effect on the proliferation of MDA-MB-231 cells than the drug pair group and ZOL group(P<0.05);with the increase of drug concentration and time,the inhibitory effect of cinnamon Aconite on the proliferation of MDA-MB-231 cells increased in a time and conc entratio dependent manner and the difference was statistically significa nt(P<0.05).All the drugs could promote the apoptosis of MDA-MB-231 cells and the effect of combined group was stronger than that of drug pair group and ZOL group(P<0.05).8.Compared with the blank control group,each group of drugs could reduce the expression of PTHrP in MDA-MB-231/MC3T3-E1 coculture environm ent and up regulate the expression of OPG and RANKL,the differences were statistically significant(P<0.05).Conclusion:Warming kidney and dredging collaterals ointment combined with ZOL can regulate the blood PTHrP and OPG levels of patients with bone metastasis of kidney deficiency type of breast cancer and relieve the pain and discomfort of patients,improve the TCM Syndromes of patien ts and improve the quality of life of patients;Warming kidney and dredging collaterals decoction caninhibit the proliferation of breast cancer cells,promote the apoptosis of breast cancer cells and regulate the growth and differentiation of breast cancer cells through OPG/RANKL pathway Osteocyteco culture microenvironment and Warming kidney and dredging collaterals therapy have significant clinical effect on bone metastasis of breast cancer with kidney deficiency syndrome,which is related to 0 PG/RANKL pathway.The clinical efficacy of treating bone metastasis of br east cancer with deficiency of kidney is significant in clinical practice by warming kidney Tongluo.The methods and mechanisms of integrated tra ditional Chinese and Western medicine for the treatment of breast cancer bone metastasis deserve further exploration and research.