Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis

草酸艾司西酞普兰与纳武单抗联合用药通过诱导细胞凋亡对肝癌细胞产生协同生长抑制作用

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作者:Vincent Chin-Hung Chen, Shao-Lan Huang, Jing-Yu Huang, Tsai-Ching Hsu, Bor-Show Tzang, Roger S McIntyre

Abstract

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.

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