草酸艾司西酞普兰联合纳武利尤单抗通过诱导细胞凋亡对肝癌细胞表现出协同的生长抑制作用。
Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis.
机构信息
Department of Psychiatry, School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi 61303, Taiwan.
出版信息
Int J Mol Sci. 2023 Aug 10;24(16):12630. doi: 10.3390/ijms241612630.
Liver cancer is one of the most lethal malignant cancers worldwide. However, the therapeutic options for advanced liver cancers are limited and reveal scant efficacy. The current study investigated the effects of nivolumab (Niv) and escitalopram oxalate (Esc) in combination on proliferation of liver cancer cells both in vitro and in vivo. Significantly decreased viability of HepG2 cells that were treated with Esc or Niv was observed in a dose-dependent manner at 24 h, 48 h, and 72 h. Administration of Esc (50 μM) + Niv (20 μM), Esc (75 μM) + Niv (5 μM), and Esc (75 μM) + Niv (20 μM) over 24 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Additionally, treatment with Esc (50 μM) + Niv (1 μM), Esc (50 μM) + Niv (20 μM), and Esc (75 μM) + Niv (20 μM) over 48 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Finally, treatment with Esc (50 μM) + Niv (1 μM), Esc (50 μM) + Niv (20 μM), and Esc (75 μM) + Niv (20 μM) for 72 h exhibited synergistic effects, inhibiting HepG2 survival. Com-pared with controls, HepG2 cells treated with Esc (50 μM) + Niv (20 μM) exhibited significantly increased sub-G1 portion and annexin-V signals. In a xenograft animal study, Niv (6.66 mg/kg) + Esc (2.5 mg/kg) significantly suppressed the growth of xenograft HepG2 tumors in nude mice. This study reports for the first time the synergistic effects of combined administration of Niv and Esc for inhibiting HepG2 cell proliferation, which may provide an alternative option for liver cancer treatment.
肝癌是全球最致命的恶性癌症之一。然而，晚期肝癌的治疗选择有限，疗效甚微。本研究旨在探讨nivolumab（Niv）和草酸依地普仑（Esc）联合应用对肝癌细胞在体外和体内增殖的影响。结果显示，Esc 或 Niv 处理 HepG2 细胞 24 h、48 h 和 72 h 后，细胞活力呈剂量依赖性下降。Esc（50 μM）+Niv（20 μM）、Esc（75 μM）+Niv（5 μM）和 Esc（75 μM）+Niv（20 μM）24 h 给药表现出协同作用，抑制 HepG2 细胞的存活。此外，Esc（50 μM）+Niv（1 μM）、Esc（50 μM）+Niv（20 μM）和 Esc（75 μM）+Niv（20 μM）48 h 给药也表现出协同作用，抑制 HepG2 细胞的存活。最后，Esc（50 μM）+Niv（1 μM）、Esc（50 μM）+Niv（20 μM）和 Esc（75 μM）+Niv（20 μM）72 h 给药也表现出协同作用，抑制 HepG2 细胞的存活。与对照组相比，Esc（50 μM）+Niv（20 μM）处理的 HepG2 细胞的 sub-G1 部分和 annexin-V 信号显著增加。在异种移植动物研究中，Niv（6.66 mg/kg）+Esc（2.5 mg/kg）显著抑制裸鼠异种移植 HepG2 肿瘤的生长。本研究首次报道了 Niv 和 Esc 联合应用抑制 HepG2 细胞增殖的协同作用，为肝癌的治疗提供了一种新的选择。
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