Protective Effect of Escitalopram on Hepatocellular Carcinoma by Inducing Autophagy

被引:14
作者
Chen, Li-Jeng [1 ]
Hsu, Tsai-Ching [1 ,2 ,3 ]
Chan, Hsiang-Lin [4 ,5 ]
Lin, Chiao-Fan [4 ,5 ]
Huang, Jing-Yu [6 ]
Stewart, Robert [7 ,8 ]
Tzang, Bor-Show [1 ,2 ,3 ,9 ]
Chen, Vincent Chin-Hung [5 ,6 ]
机构
[1] Chung Shan Med Univ, Inst Med, Taichung 40201, Taiwan
[2] Chung Shan Med Univ, Immunol Ctr, Taichung 40201, Taiwan
[3] Chung Shan Med Univ Hosp, Dept Clin Lab, Taichung 40201, Taiwan
[4] Linkou Chang Gung Mem Hosp, Dept Child Psychiat, Taoyuan 33305, Taiwan
[5] Chang Gung Univ, Sch Med, Dept Psychiat, Taoyuan 33302, Taiwan
[6] Chiayi Chang Gung Mem Hosp, Chang Gung Med Fdn, Dept Psychiat, Chiayi 61303, Taiwan
[7] Kings Coll London, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England
[8] South London & Maudsley NHS Fdn Trust, London SE5 8AZ, England
[9] Chung Shan Med Univ, Sch Med, Dept Biochem, Taichung 40201, Taiwan
关键词
hepatocellular carcinoma (HCC); selective serotonin reuptake inhibitors (SSRIs); escitalopram; autophagy; nationwide population-based cohort study; SEROTONIN REUPTAKE INHIBITORS; CANCER; ANTIDEPRESSANT; SERTRALINE; APOPTOSIS; MEDICATION; MUTATION; CELLS;
D O I
10.3390/ijms23169247
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Hepatocellular carcinoma (HCC) is an aggressive cancer with poor prognosis. Although recent research has indicated that selective serotonin reuptake inhibitors (SSRIs), including escitalopram, have anticancer effects, little is known about the effects of escitalopram on HCC. Methods: Both in vitro and in vivo studies were conducted to verify the potentials of escitalopram on HCC treatment. To explore whether the effects of escitalopram are clinically consistent with laboratory findings, a nationwide population-based cohort study was also adopted to examine the association between escitalopram and HCC risk. Results: As compared with THLE-3 cells, escitalopram significantly inhibited the proliferation of HepG2 and Huh-7 cells. Specifically, escitalopram significantly induced autophagy in HepG2 and Huh-7 cells by increasing the LC3-II/LC3-I ratio and the expression of ATG-3, ATG-5, ATG-7, and Beclin-1 proteins. Moreover, escitalopram significantly inhibited the growth of xenografted Huh-7 cells in SCID mice that were treated with 12.5 mg/kg escitalopram. Accordingly, the risk of HCC was negatively correlated with escitalopram use. Conclusions: These findings provided evidence supporting the therapeutic potential of escitalopram for HCC. Both laboratory and nationwide population-based cohort evidence demonstrated the attenuated effects of escitalopram on HCC.
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页数:16
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