Bornlisy Attenuates Colitis-Associated Colorectal Cancer via Inhibiting GPR43-Mediated Glycolysis

Xia Lu; Shuping Qiao; Chen Peng; Wenyue Yan; Zhen Xu; Junxing Qu; Yayi Hou; Shuli Zhao; Ping Chen; Tingting Wang

doi:10.3389/fnut.2021.706382

Bornlisy Attenuates Colitis-Associated Colorectal Cancer via Inhibiting GPR43-Mediated Glycolysis

Front Nutr. 2021 Nov 12:8:706382. doi: 10.3389/fnut.2021.706382. eCollection 2021.

Authors

Xia Lu¹, Shuping Qiao¹, Chen Peng¹, Wenyue Yan², Zhen Xu¹, Junxing Qu¹, Yayi Hou¹, Shuli Zhao³, Ping Chen², Tingting Wang¹

Affiliations

¹ The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
² Department of Oncology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China.
³ General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Abstract

There is evidence that probiotics have a broad antitumor effect in colorectal cancer (CRC). However, the mechanism remains obscure. Here, we investigated the effect of Bornlisy (BO)-cocktails of three probiotics on colitis-associated colon cancer (CAC) and the underlying mechanism. The treatment of CAC mice with BO resulted in decreased tumor loads as compared with their counterparts. BO also inhibited the proliferation and metastasis of CRC cells in vitro. Furthermore, BO inhibited cell proliferation through downregulating glycolysis. Activating glycolysis reversed the protective role of BO in the CAC mice. Mechanically, BO administration promoted the activation of GPR43, followed by its downstream PLC-PKC-ERK pathway, which led to decreased glucose metabolism. These results suggest that BO may provide an intervention strategy for CRC therapy, while GPR43 is a potential targeting receptor during the BO treatment.

Keywords: GPR43; colitis-associated colon cancer; glycolysis; metabolism reprogramming; probiotic.