Abstract

Hepatocellular carcinoma (HCC) still ranks among the top cancers worldwide with high incidence and mortality. Due to abnormal activation of the PI3K/AKT/mTOR signalling pathway in HCC, targeting this pathway represents a potential therapeutic strategy. NVP-BEZ235 is a novel dual-targeted ATP-competitive PI3K/mTOR inhibitor that has shown effective antitumor effects. In this study, we found that interleukin-6 (IL-6) was significantly increased after exposure to NVP-BEZ235, and we proposed a treatment in which an anti-IL-6 antibody was combined with NVP-BEZ235 for HCC. In vitro results revealed that targeted inhibition of IL-6 potentiated the antitumor effects of NVP-BEZ235 in HCC cells. The mechanism might be attributed to their synergistic inhibitory activity on the PI3K/AKT/mTOR signalling pathway. Furthermore, an in vivo study demonstrated that combined administration of NVP-BEZ235 and anti-IL-6 Ab reduced HCC tumour load more effectively than either NVP-BEZ235 or anti-IL-6 Ab treatment alone. These findings add guidance value to the analysis of HCC and provide a reference for clinical treatment.

Details

Title
The synergistic antitumor effect of IL-6 neutralization with NVP-BEZ235 in hepatocellular carcinoma
Author
Wang, Yao 1 ; Miao Xiaolong 2 ; Jiang Yuancong 2 ; Wu Zelai 2 ; Zhu Xuhang 3 ; Liu, Han 2 ; Wu, Xiaoying 4 ; Cai Jinzhen 5   VIAFID ORCID Logo  ; Ding Xianfeng 1   VIAFID ORCID Logo  ; Gong Weihua 6   VIAFID ORCID Logo 

1  Zhejiang Sci-Tech University, College of Life Sciences and Medicine, Hangzhou, China (GRID:grid.413273.0) (ISNI:0000 0001 0574 8737) 
2  Zhejiang University, Department of Surgery, Second Affiliated Hospital of School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
3  Zhejiang Cancer Hospital, Department of head and neck Surgery, Hangzhou, China (GRID:grid.417397.f) (ISNI:0000 0004 1808 0985) 
4  Tongde Hospital of Zhejiang Province, Department of Thyroid and Breast Surgery, Hangzhou City, China (GRID:grid.417168.d) (ISNI:0000 0004 4666 9789) 
5  The Affiliated Hospital of Qingdao University, Organ Transplantation Center, Qingdao, China (GRID:grid.412521.1) (ISNI:0000 0004 1769 1119); The Affiliated Hospital of Qingdao University, Liver Disease Center, Qingdao, China (GRID:grid.412521.1) (ISNI:0000 0004 1769 1119) 
6  Zhejiang University, Department of Surgery, Second Affiliated Hospital of School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University Medical Center, Liangzhu Laboratory, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
Publication year
2022
Publication date
Feb 2022
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-022-04583-5
ProQuest document ID
2628405467
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.