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缝隙连接蛋白 26 的表达通过丝裂原活化蛋白激酶信号通路调节肝癌细胞的放射敏感性。

The Expression of Connexin 26 Regulates the Radiosensitivity of Hepatocellular Carcinoma Cells through a Mitogen-Activated Protein Kinases Signal Pathway.

机构信息

Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei 230031, China.

出版信息

Int J Mol Sci. 2022 Nov 24;23(23):14644. doi: 10.3390/ijms232314644.

Abstract

Connexin 26 (Cx26) is a protein that constitutes a gap junction and is widely expressed in the liver. Abnormal expression of Cx26 is one of the important mechanisms of liver cancer, and is closely related to the transmission of radiation damage signals between cells. In the present study, we investigated the radiosensitivity of hepatocellular carcinoma (HCC) cells HepG2, with low expression of Cx26, and SK-hep-1, with high expression of Cx26 after X-ray irradiation. The cell survival, micronucleus formation and protein expressions of the mitogen-activated protein kinases (MAPK) signaling pathway were detected. The expression level of Cx26 could affect the radiosensitivity of liver cancer cells by affecting the phosphorylation of p38 and ERK proteins and regulating the expression of downstream NF-κB. Cell lines with knock-out and overexpression of Cx26 were also built to confirm the findings. Our results suggested that Cx26 might play an important role in the radiosensitivity of liver cancer and could be a potential target for clinical radiotherapy of liver cancer.

摘要

间隙连接蛋白 26(Cx26)是一种构成间隙连接的蛋白质,在肝脏中广泛表达。Cx26 的异常表达是肝癌的重要机制之一,与细胞间辐射损伤信号的传递密切相关。本研究探讨了 Cx26 低表达的肝癌细胞 HepG2 和 Cx26 高表达的 SK-hep-1 经 X 射线照射后的放射敏感性。检测了细胞存活、微核形成以及丝裂原活化蛋白激酶(MAPK)信号通路的蛋白表达。Cx26 的表达水平可通过影响 p38 和 ERK 蛋白的磷酸化以及调节下游 NF-κB 的表达来影响肝癌细胞的放射敏感性。还构建了 Cx26 敲除和过表达的细胞系以验证研究结果。我们的研究结果表明,Cx26 可能在肝癌的放射敏感性中发挥重要作用,是肝癌临床放射治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a29/9740976/13777150d0e0/ijms-23-14644-g001.jpg

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