Huang Ya-Hui, Yeh Chau-Ting
Liver Research Center, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan, Taiwan, R.O.C.;
Molecular Medicine Research Center, Chang-Gung University, Taoyuan, Taiwan, R.O.C.
Anticancer Res. 2023 Mar;43(3):1201-1206. doi: 10.21873/anticanres.16266.
BACKGROUND/AIM: An epidemiological investigation indicated that tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were associated with a lower risk of hepatocellular carcinoma (HCC). Another previous study showed that seven antidepressants inhibited glucocorticoid receptor (GR)-mediated gene transcription, a pathway that is linked to various diseases, including cancer. It is known that the expression levels of GR in cancerous tissues are higher than those in noncancerous tissues in patients with HCC. Notably, among the seven antidepressants, amitriptyline (TCA), desipramine (TCA), and fluoxetine (SSRI) were found to induce apoptosis in HCC cells. Given this, we investigated whether four other GR-specific antidepressants, including mianserin (atypical antidepressant), tianeptine (atypical antidepressant), imipramine (TCA), and moclobemide (monoamine oxidase inhibitor, MAOI) affect the cell viability of HCC.
Cell proliferation and IC curves were determined by MTT assays.
Imipramine and mianserin significantly inhibited HCC cell viability, whereas moclobemide and tianeptine did not. IC showed that the same dose of imipramine or mianserin led to significant inhibitory effects on HCC cells whereas there were only slight effects on normal human hepatocytes (HH).
According to previous and present findings, TCAs, SSRIs and mianserin may have anti-tumor activity in HCC. However, the appropriate dose, frequency, and route of the administration still need to be determined in future preclinical and clinical studies.
背景/目的：一项流行病学调查表明，三环类抗抑郁药（TCA）和选择性5-羟色胺再摄取抑制剂（SSRI）与肝细胞癌（HCC）风险降低相关。另一项既往研究显示，七种抗抑郁药可抑制糖皮质激素受体（GR）介导的基因转录，该通路与包括癌症在内的多种疾病相关。已知HCC患者癌组织中GR的表达水平高于非癌组织。值得注意的是，在这七种抗抑郁药中，发现阿米替林（TCA）、地昔帕明（TCA）和氟西汀（SSRI）可诱导HCC细胞凋亡。鉴于此，我们研究了另外四种GR特异性抗抑郁药，包括米安色林（非典型抗抑郁药）、噻奈普汀（非典型抗抑郁药）、丙咪嗪（TCA）和吗氯贝胺（单胺氧化酶抑制剂，MAOI）是否会影响HCC的细胞活力。
通过MTT法测定细胞增殖和IC曲线。
丙咪嗪和米安色林显著抑制HCC细胞活力，而吗氯贝胺和噻奈普汀则无此作用。IC结果显示，相同剂量的丙咪嗪或米安色林对HCC细胞有显著抑制作用，而对正常人肝细胞（HH）仅有轻微影响。
根据既往及当前研究结果，TCA、SSRI和米安色林可能在HCC中具有抗肿瘤活性。然而，给药的合适剂量、频率和途径仍需在未来的临床前和临床研究中确定。
