本公眾號每工作日分享一篇最新一期Anesthesia & Analgesia等SCI雜志的摘要翻譯，敬請關(guān)注并提出寶貴意見     

右美托咪啶(DEX)是臨床上廣泛使用的一種麻醉劑，據(jù)報道它在多發(fā)性實體瘤的發(fā)展過程中表現(xiàn)出矛盾的作用。在這項研究中，我們試圖探索DEX調(diào)節(jié)肝細(xì)胞癌（HCC）進展并導(dǎo)致肝纖維化的的機制。我們測定了DEX對肝纖維化小鼠原位肝癌模型腫瘤進展的影響。采用小鼠肝癌細(xì)胞(H22)與原代活化的肝星狀細(xì)胞(AHSCs)共培養(yǎng)體系和異種皮下移植模型，研究DEX對肝癌進展的影響。我們發(fā)現(xiàn)，在臨床前肝纖維化小鼠模型中，DEX治療顯著縮短了小鼠的中位生存期，促進了腫瘤生長、肝內(nèi)轉(zhuǎn)移和肺轉(zhuǎn)移。DEX受體(ADRA2A)主要在AHSCs中表達，而在HCC細(xì)胞中幾乎檢測不到。在共培養(yǎng)體系和共移植小鼠模型中，DEX均能顯著增強AHSCs對肝癌惡性行為的影響，但單獨使用DEX對肝癌的惡性程度無明顯影響。機制上，DEX通過激活STAT3誘導(dǎo)AHSCs分泌IL-6，促進肝癌進展。我們的研究結(jié)果表明，DEX的臨床應(yīng)用可能會對伴有肝纖維化的HCC患者產(chǎn)生不良副作用。

原始文獻來源：Peng Chen, Xiaojun Luo, Guanqi Dai,et al.Dexmedetomidine promotes the progression of hepatocellular carcinoma through hepatic stellate cell activation. Experimental & Molecular Medicine (2020) 52:1062–1074.

Dexmedetomidine promotes the progression of hepatocellular carcinoma through hepatic stellate cell activation

Dexmedetomidine (DEX) is an anesthetic that is widely used in the clinic, and it has been reported to exhibit paradoxical effects in the progression of multiple solid tumors. In this study, we sought to explore the mechanism by which DEX regulates hepatocellular carcinoma (HCC) progression underlying liver fibrosis. We determined the effects of DEX on tumor progression in an orthotopic HCC mouse model of fibrotic liver. A coculture system and a subcutaneous xenograft model involving coimplantation of mouse hepatoma cells (H22) and primary activated hepatic stellate cells (aHSCs) were used to study the effects of DEX on HCC progression. We found that in the preclinical mouse model of liver fibrosis, DEX treatment significantly shortened median survival time and promoted tumor growth, intrahepatic metastasis and pulmonary metastasis. The DEX receptor (ADRA2A) was mainly expressed in aHSCs but was barely detected in HCC cells. DEX dramatically reinforced HCC malignant behaviors in the presence of aHSCs in both the coculture system and the coimplantation mouse model, but DEX alone exerted no significant effects on the malignancy of HCC. Mechanistically, DEX induced IL-6 secretion from aHSCs and promoted HCC progression via STAT3 activation. Our findings provide evidence that the clinical application of DEX may cause undesirable side effects in HCC patients with liver fibrosis.