Impact of Radix Astragali Rhizoma Curcumae on the NF-κB Pathway and Tumor Autophagy in Lewis Lung Cancer Mice
Objective To investigate the mechanism of action of Radix Astragali-Rhizoma Curcumae in inhibi-ting the NF-κB pathway and inducing tumor autophagy in Lewis lung cancer mice.Methods The Lewis lung cancer mouse model was established through subcutaneous injection of Lewis cell suspension into the axillary region.After suc-cessful modeling,40 mice were assigned into four groups by random number table:model group,Chinese medicine group,cisplatin group,and Chinese medicine+cisplatin group,with 10 in each group.On the 3rd day after modelling,the cisplatin group received intraperitoneal injection of cisplatin(2 mg/kg),once every three days for a total of six doses.Additionally,they were administered sterilized double-distilled water by gavage(8.2 g/kg)daily.The Chinese medicine group received Radix Astragali Rhizoma Curcumae concentrated decoction(8.2 g/kg)by gavage,once per day for 18 consecutive days,a-long with intraperitoneal injection of diluted solution(2 mg/kg·3d).The Chinese medicine+cisplatin group was given both Chinese medicine and cisplatin following the same administration method mentioned above.For the model group,an e-quivalent volume of sterilized double-distilled water was administered by gavage,and the same diluted solution was ad-ministered via intraperitoneal injection on a daily basis.Throughout the study period,the mice were observed for changes in hair,activity,food consumption,and water intake.The body mass of the mice was measured every two days,and the tumor volume was measured every four days.After 20 days of tumor modeling,the protein expressions of NF-κB p65,p-NF-κB p65,IκB-α,p-IκB-α,LC3,and Beclin-1 in the tumor tissues were assessed through Western Blot.Additionally,the levels of TNF-α and IL-1 β in the tumor tissues were determined using ELISA.The ultramorphological changes of tumor cells were examined by transmission electron microscopy.Results Compared with the model group,the Chinese medicine group showed no significant difference in body mass(P>0.05),while the cisplatin and Chinese medicine+cis-platin groups exhibited significantly lower body mass(P<0.01).The tumor volume was reduced(P<0.01),and LC3-Ⅱ/LC3-Ⅰ and Beclin-1/β-actin were up-regulated in all treatment groups(P<0.01),while p-NF-κB p65/NF-κB p65,pIκBα/IκBα,TNF-α,and IL-1β were down-regulated(P<0.05).Compared with the cisplatin group,the Chinese medicine+cisplatin group had no obvious difference in tumor volume and LC3-Ⅱ/LC3-Ⅰ(P>0.05),but had increased Beclin-1/β-actin(P<0.01)and decreased p-NF-κB p65/NF-κB p65,pIκBα/IκBα,TNF-α,and IL-1β(P<0.05).The Chinese medicine+cisplatin group had lower body mass(P<0.01),smaller tumor volume(P<0.01),higher Beclin-1/β-actin(P<0.01),and lower p-NF-κB p65/NF-κB p65,pIκBα/IκBα,TNF-α,and IL-1β(P<0.05)than the Chinese medicine group.The difference in LC3-Ⅱ/LC3-Ⅰ was not significant between the two groups(P>0.05).Conclusion Radix Astragali Rhizoma Curcumae has the ability to inhibit the activation of NF-κB and improve the inflammatory microenvironment of tumors.This is achieved by reducing the degradation of IκB-α through the inhibition of its phosphorylation.Moreover,the combination up-regulates the expression of autophagy-related proteins and induces cellular autophagy,ultimately leading to the inhibition of tumor growth.