Title:Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal
Cell Carcinoma
Volume: 24
Issue: 10
Author(s): Yue Chong, Shan Xu, Tianjie Liu, Peng Guo, Xinyang Wang, Dalin He*Guodong Zhu*
Affiliation:
- Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China
- Oncology
Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an,
710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi’an Jiaotong University, Xi’an,
710061, China
- Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China
- Oncology
Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an,
710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi’an Jiaotong University, Xi’an,
710061, China
Keywords:
Renal cell carcinoma, vasculogenic mimicry, metastasis, curcumin, ETS-1, VE-Cadherin, MMP9.
Abstract:
Background: Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has
become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system
formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies,
curcumin has been demonstrated to play antineoplastic effects in many different types of human
cancers; however, its function and mechanism of targeting VM in RCC remains unknown.
Objective: Here, in the work, we explored the role of curcumin and its molecular mechanism in
the regulation of VM formation in RCC.
Methods: RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect
E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase
9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen
the differential expressed genes. Plasmid transfections were used to transiently knock down or
overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments.
CD31-PAS double staining was used to label the VM channels in patients and xenograft
samples.
Results: Our results demonstrated that VM was positively correlated with RCC grades and stages
using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner
in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional
factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased
the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9.
Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression
both
in vitro and
in vivo.
Conclusion: Our finding might indicate that curcumin could inhibit VM by regulating ETS-1,
VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential
anti-cancer compound by inhibiting VM in RCC progression.