The Synergistic Antitumor Effect of IL-6 Neutralization with NVP-BEZ235 in Hepatocellular Carcinoma

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2022 Feb 15

PMID 35165269

Authors

Yao Wang

Xiaolong Miao

Yuancong Jiang

Zelai Wu

Xuhang Zhu

Han Liu

Xiaoying Wu

Jinzhen Cai

Xianfeng Ding

Weihua Gong

Affiliations

Soon will be listed here.

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.

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