Zhang Jian, Shan Wei-feng, Jin Te-te, Wu Guo-qing, Xiong Xiao-Xing, Jin Hai-yan, Zhu Sheng-mei
Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, People's Republic of China.
J Transl Med. 2014 Oct 9;12:279. doi: 10.1186/s12967-014-0279-x.
We previously confirmed that propofol directly inhibited the viability, proliferation, and invasiveness of hepatocellular carcinoma cells in vitro. In this study, we investigated the mechanism underlying the anti-HCC effects of propofol.
In vivo antitumor activity was investigated in tumor-bearing mice following an intraperitoneal injection of propofol, with or without clodrolip. The co-culture system was used to verify that miR-142-3p was transported from macrophages to HCC cells. A miR-142-3p inhibitor was used to down-regulate the expression of miR-142-3p.
Propofol drastically inhibited tumor growth in tomor-bearing mice through macrophage activation, and stimulated tumor-associated macrophages (TAMs) to secrete microvesicles (MVs), which delivered miR-142-3p to HCC cells, resulting in the inhibition of HCC cell invasion. In addition, MVs collected from the plasma of the tumor-bearing mice injected with propofol suppressed tumor growth. More importantly, down-regulation of the expression miR-142-3p reversed the effect of propofol on HCC cell migration.
This study reveals a novel role for propofol in the inhibition of HCC through MV-mediated transfer of miR-142-3p from macrophages to cancer cells in vivo.
我们之前证实丙泊酚在体外可直接抑制肝癌细胞的活力、增殖及侵袭能力。在本研究中，我们探究了丙泊酚抗肝癌作用的潜在机制。
对荷瘤小鼠腹腔注射丙泊酚（有无氯屈膦酸脂质体），研究其体内抗肿瘤活性。采用共培养系统验证miR-142-3p从巨噬细胞转运至肝癌细胞。使用miR-142-3p抑制剂下调miR-142-3p的表达。
丙泊酚通过激活巨噬细胞显著抑制荷瘤小鼠的肿瘤生长，并刺激肿瘤相关巨噬细胞（TAM）分泌微泡（MV），后者将miR-142-3p传递至肝癌细胞，从而抑制肝癌细胞侵袭。此外，从注射丙泊酚的荷瘤小鼠血浆中收集的微泡可抑制肿瘤生长。更重要的是，下调miR-142-3p的表达可逆转丙泊酚对肝癌细胞迁移的作用。
本研究揭示了丙泊酚在体内通过微泡介导miR-142-3p从巨噬细胞转移至癌细胞从而抑制肝癌方面的新作用。
