Journal
JOURNAL OF CANCER
Volume 7, Issue 8, Pages 935-946Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.13628
Keywords
Hepatitis B virus X protein(HBx); Alpha fetoprotein(AFP); Hepatocarcinogenesis; Malignant behaviors
Categories
Funding
- National Natural Science Foundation of China [81560450, 31560243, 81360307, 81260306, 81160261, 31060164, 30960153]
- Project of Hainan Province Innovative Team [2016CXTD008]
- Key Projects of Science and Technology, Hainan Province [ZDXM 20110038]
- Natural Science Foundation of Hainan Province [309034, 310044, 814293]
- Fund of Hainan Provincial Society Development [2015SF03]
- Hainan Provincial Department of Education [HjKj 2013-21]
- Hainan Provincial Association for Science and Technology program of Youth Science Talent and Academic Innovation [201514]
- Haikou Key Program of Science Technology [2014062]
- [Hnkyzx2014-07]
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Background: The infection of Hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma(HCC), HBV-X protein(HBx) is able to induce expression of alpha-fetoprotein(AFP) in normal liver cells, and AFP harbors a function to promote malignant transformation of normal liver cells, but the role AFP playing in malignant behaviors of HCC cells is still unclear. Methods: Fifty-six liver tissue samples were collected from the clinical patients through hepatectomy(include normal liver tissues, HBV-related hepatitis liver tissues and HBV-related HCC tissues), and diagnosis of these tissues by pathology section, expression of AFP, Ras and CXCR4 were evidenced by immunohisochemical staining and Western blotting; The proliferation of human normal liver cells line L-02 cells and human hepatoma cells line, HLE cells(non AFP-producing) were performed by MTT method; Repaired capacity of L-02 and HLE cells were compared by wound healing assay; Migration and invasion of these cells were analyzed by Transwell chamber assay; HBx expressed vectors(pcDNA3.1-HBx) were constructed and transfected into L-02 and HLE cells, effects of pcDNA3.1-HBx on the malignant behaviors were also detected by MTT, Transwell chamber assay and the expression of AFP, Ras and CXCR4 were evidenced by Western blotting. Results: we found that expression of AFP, Ras and CXCR4 in HBV-related HCC and lymph nodes metastasis tissues were significantly elevated compared with HBV-related HCC, non metastasis tissues and HBV-related hepatitis tissues; Expression of AFP, Ras and CXCR4 in HBV-related hepatitis tissues were significantly enhanced compared with normal liver tissues; The growth ratio, migratory and invasive ability, expression of AFP, Ras and CXCR4 of the cells were outstanding promoted while L-02 and HLE cells were transfected with pcDNA3.1-HBx vectors. The proliferation ratio, migration and invasion ability, and expression of Ras and CXCR4 were significantly inhibited while L-02-X and HLE-X cells(stably transfected with pcDNA3.1-HBx) were silenced AFP expression by AFP-siRNA. Conclusions: HBx through stimulating expression of AFP to promote malignant behaviors of human normal liver cells and HCC cells; AFP maybe used as a novel biotarget for therapeutics of HCC patients.
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