Nebivolol Inhibits Hepatocellular Carcinoma via RHOQ and Enhances the Efficacy of Lenvatinib
Saihua Zhang1, Hechun Lin1, Junming Yu1
1State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 25/Ln 2200 Xietu Road, Shanghai 200032, China.
Abstract:
Hepatocellular carcinoma (HCC) is associated with high mortality due to late diagnosis, recurrence, and limited therapeutic options. Thus, there is an urgent need for novel treatment approaches and new therapeutic targets. Cardiotoxicity resulting from anticancer therapies has become increasingly prominent, leading to a higher risk of cardiovascular diseases among cancer survivors. In our study, through a drug library screening, we identified that the cardiovascular therapeutic agent nebivolol exerts antitumor effects against HCC both in vivo and in vitro. Mechanistically, nebivolol suppressed HCC progression by downregulating RHOQ independently of β1-adrenergic receptors. Furthermore, the combination of nebivolol and lenvatinib synergistically inhibited HCC proliferation both in vivo and in vitro. This study provides a rationale for repurposing nebivolol as a combination strategy for HCC therapy.
Insights
The cardiovascular drug nebivolol shows antitumor effects against hepatocellular carcinoma (HCC). Combining nebivolol with lenvatinib synergistically inhibits HCC progression, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) presents significant mortality due to late diagnosis and limited treatment options.
- Anticancer therapies can cause cardiotoxicity, increasing cardiovascular disease risk in survivors.
- Novel therapeutic targets and approaches are crucial for effective HCC management.
Purpose of the Study:
- To identify novel therapeutic agents for hepatocellular carcinoma (HCC).
- To investigate the potential of repurposing cardiovascular drugs for HCC treatment.
- To explore combination therapy strategies for enhanced HCC inhibition.
Main Methods:
- Drug library screening to identify potential HCC therapeutic agents.
- In vitro and in vivo experiments to evaluate nebivolol's antitumor effects.
- Mechanistic studies to elucidate nebivolol's mode of action in HCC.
- Combination studies with lenvatinib to assess synergistic effects.
Main Results:
- Nebivolol demonstrated significant antitumor activity against HCC in vitro and in vivo.
- Nebivolol suppressed HCC progression by downregulating RHOQ, independent of beta1-adrenergic receptors.
- The combination of nebivolol and lenvatinib exhibited synergistic inhibition of HCC proliferation.
Conclusions:
- Nebivolol exhibits potent anti-HCC effects, suggesting its repurposing potential.
- Nebivolol's mechanism involves RHOQ downregulation, offering a novel therapeutic target.
- Combination therapy with nebivolol and lenvatinib provides a promising synergistic strategy for HCC treatment.
Related Concept Videos
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:31Adrenergic Antagonists: ɑ and β-Receptor Blockers
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...