理冲生髓饮治疗卵巢癌作用及机制研究OA

Objective:To explore the relevant mo-lecular mechanism of Lichong Shengsui Decoction(理冲生髓饮)exerting anti-ovarian cancer(OC)effects by regulating the nuclear factor-κB(NF-κB)pathway mediated by tripartite motif-containing protein 44(TRIM44).Methods:Human ovarian cancer SKOV3 cells with stable overexpression of TRIM44 were constructed,and the cells were subcutaneously inoculated into Balb/C nude mice to establish a xenograft tumor model.A total of 40 nude mice were randomly divided into the blank group,cisplatin group,Chinese medicinal group,and combination group,with 10 mice in each group.The Chinese medicinal group was given Lichong Shengsui Decoction at a dose of 7.52 g/kg by gavage twice a day.The cisplatin group was intraperitoneally injected with 0.1 mg/mL cisplatin solution every other day.The combination group was given Lichong Shengsui Decoction at 7.52 g/kg by gavage twice a day,combined with intraperitoneal injection of 0.1 mg/mL cisplatin solution(equivalent to 3 mg/kg)every other day.The blank group was given an equal volume of normal saline by gavage twice a day.After 14 days of drug intervention,the tumor volume and growth trend of nude mice were observed.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes of tumor tissues.Reverse transcription-polymerase chain reaction(RT-PCR)was employed to detect the mRNA expressions of inhibitor of κB kinase β(IκKβ),nuclear factor-κB inhibitorα(IκBα),and nuclear factor-κB p65(NF-κB p65)in tumor tissues.Double immunofluorescence staining was used to detect the distribution of TRIM44 and NF-κB p65 proteins in tumor tissues.Western blot(WB)was applied to determine the differences in the protein expressions of TRIM44,IκKβ,IκBα,phosphorylated nuclear factor-κB inhibitor α(p-IκBα),NF-κB p65,B-cell lymphoma-2(Bcl-2),matrix metalloproteinase-9(MMP-9),cysteinyl aspartate-specific protease 3(Caspase3),and vascular endothelial growth factor(VEGF)in tumor tissues.Results:Compared with the blank group,the cisplatin group,Chinese medicinal group,and combination group all inhibited the growth of ovarian cancer xenografts in nude mice.All medication groups were able to reduce the mRNA expressions of IκKβ and NF-κB p65 in tumor tissue,and up-regulate the mRNA expression of IκBα in tumor tissues,with the most significant difference in the combination group(P＜0.05).All medication groups significantly decreased the protein expressions of TRIM44,IκKβ,p-IκBα,NF-κB p65,Bcl-2,MMP-9,VEGF,and increased the protein expressions of IκBαand Caspase-3 in tumor tissues,with the most prominent effect in the combination group(P＜0.05).Conclusions:Lichong Shengsui Decoction can inhibit the growth of ovarian cancer xenografts in nude mice and enhance anti-tumor effects in combination with cisplatin.Its mechanism may be related to down-regulating the expression of TRIM44,inhibiting the activation of the NF-κB signaling pathway,thereby suppressing the invasion and metastasis of ovarian cancer and promoting its apoptosis.