title: KRT6B, a key mediator of notch signaling in honokiol-induced human hepatoma cell apoptosis.
abstract: The study was performed to investigate the relationship between KRT6B and Notch1 in the development and progress of hepatocellular carcinoma. The cell viability was detected by CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining on a flow cytometry. Expression of genes and proteins were analyzed by real-time PCR and Western blotting, respectively. KRT6B gene was overexpressed using a lentiviral expression vector in a human hepatoma cell line in vitro, in order to explore the mechanism by which the KRT6B promoted cell growth. The results of CCK8 and immunohistochemistry showed that honokiol induced cell death in a concentration- dependent manner, and suppressed human hepatoma cells' proliferation. The mRNA and protein expression of Notch1 was significantly lower in human hepatoma cells with honokiol treatment than that in the untreatment group. Activation of Notch-1 by exogenous transfection of Notch1 intracellular domain increased KRT6B expression in human hepatoma cells. Furthermore, cells were transfected with the wild type pLenti-KRT6B vector, the protein expression of KRT6B and NOTCH1 was significantly upregulated in human hepatoma cells with honokiol treatment. Overexpression of KRT6B promoted hepatoma cells' proliferation and showed anti-apoptosis effect. This study demonstrated that honokiol could induce human hepatoma cells' apoptosis. KRT6B, a key mediator of Notch signaling, was downregulated in honokiol-induced hepatocellular carcinoma apoptosis, suggesting that KRT6B might be a novel therapeutic target for the treatment of hepatocellular carcinoma.
authors.affiliation: Faculty of Basic Medicine, Bengbu Medical College Bengbu, China.
authors.forename: Haoxuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College Bengbu, China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Huo
authors.affiliation: Laboratory Diagnostics Division, Changhai Hospital Affiliated to Second Military Medical University Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pathology, Anhui Provincial Hospital Hefei, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Xu
keywords: Krt6b; Notch1; hepatocellular carcinoma; honokiol