Preclinical Evidence that Arctigenin Effectively and Selectively Targets Clear Cell Renal Cell Carcinoma Via Suppressing EGFR and RhoA

Abstract

Clear cell renal cell carcinoma (ccRCC) has poor clinical outcomes and necessitates new treatment options. Epidermal growth factor receptor (EGFR) is a potential therapeutic target, due to the associations with various carcinomas’ progression. Arctigenin, a natural compound of Arctium lappa, has been shown to display anticancer abilities in various carcinomas. Cellular assays and combination studies were conducted using arctigenin and anti-ccRCC drugs. In vivo efficacy of arctigenin was determined using ccRCC xenograft mouse model. Immunoblotting and biochemistry analysis were applied to investigate the signaling affected by arctigenin. Arctigenin inhibits growth, migration, and survival of ccRCC cells while sparing normal kidney cells. Arctigenin acts synergistically with 5-FU and sorafenib but not temsirolimus in inhibiting ccRCC cells. Synergism of arctigenin with 5-FU and sorafenib was further shown in ccRCC xenograft mouse model. The combination of arctigenin with clinical anti-RCC drugs completely inhibits tumor growth without tumor progression even for an extended time period. Mechanistically, arctigenin inhibits migration in a RhoA-dependent manner while inhibits growth via suppressing EGFR-mediated signaling pathways. Our findings suggest that arctigenin performs well to add to current treatment in ccRCC and confirm the value to target EGFR to improve therapy in RCC.

Authors’ Contribution

Mingwei Xu conceived and designed the experiments, and supervised the project. Dongcao Liu and Guang Zhou performed the experiments and wrote the manuscript. All authors analyzed and interpreted the data, revised and approved the final manuscript.

Disclosure Statement

All authors declare no conflict of interest.

Research Involving Human Participants and/or Animals

This work was approved by the institutional review board of Xiangyang Central Hospital on 28/12/2016 (Approval Number 2018-027). This study was conducted in accordance with the Declaration of Helsinki.

Availability of Data and Materials

The data will be made available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by research grants provided Science and Technology Department of Hubei Province (Grant No. EK2017H18011668126).