Protective Effect of Banxia Xiexin Decoction on AOM/DSS-induced Colitis Associated Cancer Mice
10.13748/j.cnki.issn1007-7693.20230163
- VernacularTitle:半夏泻心汤对AOM/DSS致炎症相关性结直肠癌小鼠的保护作用
- Author:
Yinzi YUE
1
;
Yunhui GU
1
;
Yuanyuan QIN
2
;
Lianlin SU
3
;
Xiaodong HUA
4
;
Yahui WANG
4
;
Xiaoman LI
3
;
Xiaopeng WANG
4
;
Shuai YAN
4
Author Information
1. Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine Department of Anorectal Surgery
2. Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine Department of Pharmacy
3. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
4. Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine Department of Anorectal Surgery, Suzhou 215009, China
- Publication Type:Journal Article
- Keywords:
Banxia Xiexin decoction ；colitis-associated cancer； nuclear factor kappa B； macrophage； epithelial-mesenchymal transition
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(7):917-926
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism.
METHODS
Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group.
RESULTS
There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant.
CONCLUSION
BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.
