Neferine Suppresses Experimental Colitis-Associated Colorectal Cancer by Inhibition of NF-κ B p65 and STAT3

Zhou，Yishan1; Xiang，Shuangli1; Zheng，Haoyi2,3; Hou，Ying2,3; Wang，Ying2,3; Li，Chuang Chuang5; Wu，Qin1; Shi，Jingshan1; Chen，Xiuping2,3,4

2022

10.1142/S0192415X22500598

AMERICAN JOURNAL OF CHINESE MEDICINE   Impact Factor & Quartile

0192-415X

1793-6853

Colitis is an important risk factor for the development of colorectal cancer (CRC). The inhibitory effect and the underlying mechanism of neferine on colitis-associated colorectal cancer (CA-CRC) were investigated using an azoxymethane (AOM)/dextran sulfate sodium (DSS) triggered mice model. Compared with the CA-CRC model, oral treatment of neferine (2.5 and 5.0 mg/kg) significantly inhibited the DAI scores, decreased the tumor number, and reduced the tumor size. Neferine decreased inflammatory cell infiltration and epithelial hyperplasia in colon tissues. The levels of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), and interleukin 6 (IL-6) in colon tissues were decreased by neferine. Furthermore, neferine significantly decreased protein expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), p-p65, and p-STAT3 in both tumor and non-tumor tissues. In addition, neferine inhibited LPS and IL-6-induced phosphorylation of both NF-κB p65 and STAT3. Molecular docking demonstrated the interactions of neferine with both NF-κB p65 and STAT3. In conclusion, these results suggested that neferine inhibited CA-CRC carcinogenesis possibly by regulating NF-κB and STAT3. Neferine might be a lead compound for the chemoprevention of CA-CRC.

Colitis-Associated Colorectal Cancer Neferine NF-κ B p65 STAT3

SCI

English

Others

Science and Technology Development Fund, Macau SAR["SKL-QRCM(UM)-2020-2022","0081/2021/A2"] ; National First-Class Discipline Construction Project of Pharmacy[GNYL[2017]006]

Integrative & Complementary Medicine ; General & Internal Medicine

Integrative & Complementary Medicine ; Medicine, General & Internal

WOS:000838671600012

WORLD SCIENTIFIC PUBL CO PTE LTD

CLINICAL MEDICINE

2-s2.0-85133002999

Scopus

1.Key Lab for Pharmacology of Ministry of Education,Department of Pharmacology,Zunyi Medical University,Zunyi,563003,China
2.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Avenida da Universidade,999078,Macao
3.Department of Pharmaceutical Sciences,Faculty of Health Sciences,999078,Macao
4.MoE Frontiers Science Center for Precision Oncology,University of Macau,999078,Macao
5.Shenzhen Grubbs Institute and Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China

Zhou，Yishan,Xiang，Shuangli,Zheng，Haoyi,et al. Neferine Suppresses Experimental Colitis-Associated Colorectal Cancer by Inhibition of NF-κ B p65 and STAT3[J]. AMERICAN JOURNAL OF CHINESE MEDICINE,2022,50(05).

Zhou，Yishan.,Xiang，Shuangli.,Zheng，Haoyi.,Hou，Ying.,Wang，Ying.,...&Chen，Xiuping.(2022).Neferine Suppresses Experimental Colitis-Associated Colorectal Cancer by Inhibition of NF-κ B p65 and STAT3.AMERICAN JOURNAL OF CHINESE MEDICINE,50(05).

Zhou，Yishan,et al."Neferine Suppresses Experimental Colitis-Associated Colorectal Cancer by Inhibition of NF-κ B p65 and STAT3".AMERICAN JOURNAL OF CHINESE MEDICINE 50.05(2022).