Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal Cell Carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Metastatic renal cell carcinoma (RCC) presents a significant clinical challenge, particularly upon developing resistance to targeted therapies.
• Vasculogenic mimicry (VM), a tumor-driven vascularization process, enables cancer cells to bypass conventional treatments.
• The therapeutic potential of curcumin, a natural compound, against VM in RCC remains largely unexplored.

Purpose of the Study:

• To investigate the role and molecular mechanisms of curcumin in regulating VM formation in renal cell carcinoma.
• To identify key molecular targets involved in curcumin's anti-VM effects in RCC.

Main Methods:

• Utilized RNA-sequencing, immunoblotting, and immunohistochemistry to analyze gene and protein expression (ETS-1, VE-Cadherin, MMP9) in RCC cells and tissues.
• Employed plasmid transfections for knockdown and overexpression of ETS-1 to assess its role in VM.
• Quantified VM formation through in vitro tube formation assays and in vivo animal experiments, with CD31-PAS double staining for channel identification.

Main Results:

• VM formation was found to be positively correlated with RCC grade and stage in clinical samples.
• Curcumin demonstrated dose- and time-dependent inhibition of VM formation in vitro.
• RNA-sequencing identified ETS-1 as a key regulator of VM; its modulation affected VE-Cadherin and MMP9 expression and subsequent VM.
• Curcumin suppressed VM by inhibiting ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo.

Conclusions:

• Curcumin inhibits VM in RCC by downregulating the expression of ETS-1, VE-Cadherin, and MMP9.
• These findings suggest curcumin as a potential therapeutic agent for inhibiting VM and controlling RCC progression.