Ursolic Acid Protects Against Proliferation and Inflammatory Response in LPS-Treated Gastric Tumour Model and Cells by Inhibiting NLRP3 Inﬂammasome Activation

Zixi Chen; Qiaoli Liu; Zhaowei Zhu; Fenfen Xiang; Mengzhe Zhang; Rong Wu; Xiangdong Kang

doi:10.2147/CMAR.S264070

Ursolic Acid Protects Against Proliferation and Inflammatory Response in LPS-Treated Gastric Tumour Model and Cells by Inhibiting NLRP3 Inﬂammasome Activation

Cancer Manag Res. 2020 Sep 11:12:8413-8424. doi: 10.2147/CMAR.S264070. eCollection 2020.

Authors

Zixi Chen^#¹, Qiaoli Liu^#¹, Zhaowei Zhu¹, Fenfen Xiang¹, Mengzhe Zhang¹, Rong Wu¹, Xiangdong Kang¹

Affiliation

¹ Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, People's Republic of China.

^# Contributed equally.

Abstract

Background: Inflammation is considered as one of the hallmarks of cancer development and progression. Ursolic acid (UA) showed strong effects as an anti-inflammatory and antioxidant. However, the anti-cancer effects of ursolic acid require further study.

Methods: This study aimed to investigate the role of ursolic acid in a lipopolysaccharide (LPS)-treated gastric tumour mouse model and in a human gastric carcinoma cell line (BGC-823 cells). This study also aimed to confirm whether ursolic acid can protect against proliferation and the inflammatory response induced by LPS, by inhibiting the activation of the NLRP3 inflammasome via the NF-κB pathway.

Results: The present study demonstrated that ursolic acid significantly attenuated LPS-treated proliferation in a gastric tumour mouse model and the human gastric carcinoma BGC-823 cell line, reduced the expression of the NLRP3 inflammasome and suppressed the release of pro-inflammatory cytokines. In addition, ursolic acid inhibited the LPS-induced activation of NF-κB. Furthermore, the NF-κB pathway regulated the activation of the NLRP3 inﬂammasome.

Conclusion: In conclusion, these results demonstrated that ursolic acid could suppress proliferation and the inflammatory response in an LPS-induced mouse gastric tumour model and human BGC-823 cells by inhibiting the activation of the NLRP3 inﬂammasome via the NF-κB pathway. This indicates that ursolic acid can be a potential therapeutic agent for the treatment of gastric cancer.

Keywords: NF-κB pathway; NLRP3 inflammasome; gastric carcinoma; inflammatory; proliferation; ursolic acid.

Grants and funding

This work was supported by the National Natural Science Foundation of China 31800988 (Z.X. Chen), Personnel Training Program Funded by Putuo Hospital affiliated to Shanghai University of Chinese Medicine 2017216A (Z.X. Chen).