The selective serotonin reuptake inhibitors enhance the cytotoxicity of sorafenib in hepatocellular carcinoma cells.

Anticancer Drugs

Department of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Published: September 2021

Sertraline and fluoxetine are the two most commonly used selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. Accumulating evidence has revealed that SSRIs can reduce the risk of hepatocellular carcinoma (HCC), but their therapeutic effects in HCC have not yet been elucidated. Previous studies have reported that sertraline and fluoxetine can suppress the growth of gastric carcinoma, melanoma and nonsmall cell lung cancers by inhibiting the mammalian target rapamycin (mTOR) activity. In this study, we found that sertraline and fluoxetine blocked the protein kinase B (AKT)/mTOR pathway and suppressed the growth of HCC cells in vitro, in xenografts and in diethylnitrosamine/carbon tetrachloride (DEN/CCL4)-induced primary liver mouse model. Sertraline and fluoxetine can synergize with sorafenib, the first approved standard therapy for advanced HCC, to inhibit the viability of HCC cells in vitro and in vivo. In addition, the combination of sorafenib and SSRIs synergistically inhibited the effects of the AKT/mTOR pathway. These results reveal novel therapeutic effects of a combination of SSRIs and sorafenib in HCC.

Download full-text PDF

Source
http://dx.doi.org/10.1097/CAD.0000000000001067DOI Listing

Publication Analysis

Top Keywords

sertraline fluoxetine
16
selective serotonin
8
serotonin reuptake
8
reuptake inhibitors
8
hepatocellular carcinoma
8
therapeutic effects
8
akt/mtor pathway
8
hcc cells
8
cells vitro
8
hcc
6

Similar Publications

Background: This study evaluated the impact of 2015/2016 prescribing guidance on antidepressant prescribing choices in children.

Methods: A retrospective e-cohort study of whole population routine electronic healthcare records was conducted. Poisson regression was undertaken to explore trends over time for depression, antidepressant prescribing, indications and secondary care contacts.

View Article and Find Full Text PDF

Purpose: This study investigates the potential association between commonly prescribed psychotropic medications, such as Atypical Antipsychotics (AAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), and congenital anomalies in newborns. The analysis uses data from the Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: Spontaneously reported cases of congenital anomalies in newborns (under 28 days old) were extracted from the FAERS database, covering January 2004 to June 2023.

View Article and Find Full Text PDF

Major depressive disorder (MDD) and diabetes mellitus (DM) remain among the most prevalent diseases and the most significant challenges faced by medicine in the 21st century. The frequent co-occurrence and bidirectional relationship between the two conditions necessitates the identification of treatment strategies that benefit both. The purpose of this study was to systematically review and meta-analyze data on the efficacy and safety of agomelatine (AGO) in the treatment of patients with depression with comorbid diabetes to explore its potential mechanism of action in both diseases and its impact on diabetic parameters.

View Article and Find Full Text PDF

Background: Adverse cutaneous drug reactions have been reported with most drugs, including antidepressants (ADs) and second-generation antipsychotics (SGAs). The lack of extensive research on the relationship between ADs and SGAs, and cutaneous toxicity remains troubling. Our study aimed to assess the cutaneous toxicity of ADs and SGAs and provide valuable insights for clinical applications and scientific investigations.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!