尼古丁是烟草的主要成分，是诱发肝细胞癌（HCC）发生的重要因素之一。 β2-肾上腺素能受体（β2-AR）与肿瘤的生长和进展有关。然而，β2-AR 及其介导的级联在尼古丁诱导的 HCC 中的作用仍不清楚。本研究旨在观察尼古丁对永生化人肝上皮（THLE-2）细胞增殖、迁移和侵袭的影响，并探讨其潜在作用机制。细胞计数试剂盒8（CCK-8）检测结果显示，0.3125μM尼古丁具有促进THLE-2细胞增殖的能力，且具有显着的时间依赖性。因此，后期主要选择THLE-2细胞进行0.3125μM尼古丁慢性处理引起转化。 THLE-2细胞经0.3125μM尼古丁处理30代后，长期暴露于尼古丁显着增强细胞的增殖、转移和侵袭。此外，它还上调细胞内β2-AR、磷酸肌醇3激酶（PI3K）、AKT、基质金属蛋白酶-2（MMP-2）和Cyclin D1的水平，并下调p53的表达。更重要的是，β2-AR/PI3K/AKT通路被发现介导THLE-2细胞中MMP-2、Cyclin D1和p53的表达，在持续暴露于THLE-2细胞后，在其增殖、迁移和侵袭中发挥着至关重要的作用。尼古丁。简而言之，证明了β2-AR/PI3K/AKT通路在尼古丁诱导的THLE-2细胞转化中的作用。这项研究可以为尼古丁与肝癌之间的关系提供有价值的见解。此外，它还为研究与烟草消费相关的肝癌的潜在抗癌疗法奠定了基础。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Nicotine, the primary constituent of tobacco, is one of the important factors that induce the occurrence of hepatocellular carcinoma (HCC). The β2-adrenergic receptor (β2-AR) is implicated in the growth and advancement of tumors. However, the role of β2-AR and its mediated cascades in nicotine-induced HCC remains unclear. This present study aims to observe the effects of nicotine on the proliferation, migration, and invasion of immortalized human liver epithelial (THLE-2) cells, as well as to explore the underlying mechanisms of action. The results of cell counting kit-8 (CCK-8) assay showed that 0.3125μM nicotine had the ability to promote the proliferation of THLE-2 cells with a significant time-dependent manner. Therefore, THLE-2 cells were mainly selected for chronic treatment with 0.3125μM nicotine in the later stage to cause transformation. After 30 passages of THLE-2 cells with 0.3125μM nicotine treatment, chronic exposure to nicotine significantly enhanced the proliferation, metastasis, and invasion of cells. Besides, it also upregulated the intracellular levels of β2-AR, phosphoinositide 3-kinase (PI3K), AKT, matrix metalloproteinase-2 (MMP-2) and Cyclin D1, as well as downregulated the expression of p53. More importantly, the β2-AR/PI3K/AKT pathway was found to mediate the expression of MMP-2, Cyclin D1, and p53 in THLE-2 cells, playing a crucial role in their proliferation, migration, and invasion after continuous exposure to nicotine. Simply put, it demonstrated the role of β2-AR/PI3K/AKT pathway in the transformation of THLE-2 cells induced by nicotine. This study could provide valuable insights into the relationship between nicotine and HCC. Additionally, it lays the groundwork for investigating potential anticancer treatments for liver cancer linked to tobacco consumption.Copyright © 2024 Elsevier B.V. All rights reserved.