RGD Reference Report - Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo. - Rat Genome Database

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Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo.

Authors: Zhu, Huaqi  Sun, Qiman  Tan, Changjun  Xu, Min  Dai, Zhi  Wang, Zheng  Fan, Jia  Zhou, Jian 
Citation: Zhu H, etal., Mol Med Rep. 2014 Aug;10(2):585-92. doi: 10.3892/mmr.2014.2302. Epub 2014 Jun 5.
RGD ID: 151893463
Pubmed: (View Article at PubMed) PMID:24912495
DOI: Full-text: DOI:10.3892/mmr.2014.2302

The aim of our study was to elucidate the effect of tacrolimus (FK506) and of C-X-C chemokine receptor type 4 (CXCR4), which is a receptor specific to the stromal cell-derived factor-1α (SDF‑1α), on growth and metastasis of hepatocellular carcinoma (HCC). Following treatment with different concentrations of FK506, AMD3100 or normal saline (NS), the proliferation of Morris rat hepatoma 3924A (MH3924A) cells was measured by the MTT assay, the expression of CXCR4 was analyzed with immunohistochemistry, and the morphological changes and the invasiveness of cells were studied with a transwell assay and under a scanning electron microscope, respectively. In addition, August Copenhagen Irish rat models implanted with tumor were used to examine the pathological changes and invasiveness of tumor in vivo, the expression of CXCR4 in tumor tissues and the expression of SDF‑1α in the adjacent tissues to the HCC ones, using immunohistochemistry. In vitro, FK506 (100‑1,000 µg/l) significantly promoted the proliferation of MH3924A cells (P<0.01), and increased the expression of CXCR4 in MH3924A cells, albeit with no significance (P>0.05). By contrast, AMD3100 had no effect on the proliferation of MH3924A cells, but significantly reduced the expression of CXCR4 (P<0.05). The invasiveness of MH3924A cells was significantly (P<0.01) enhanced following treatment with FK506, SDF‑1α, FK506 + AMD3100, FK506 + SDF‑1α or FK506 + AMD3100 + SDF‑1α. In vivo, tumor weight (P=0.041), lymph node metastasis (P=0.002), the number of pulmonary nodules (P=0.012), the expression of CXCR4 in tumor tissues (P=0.048) and that of SDF‑1α in adjacent tissues (P=0.026) were significantly different between the FK506-treated and the NS group. Our results suggest that FK506 promotes the proliferation of MH3924A cells and the expression of CXCR4 and SDF‑1α in vivo. Therefore, inhibiting the formation of the CXCR4/SDF‑1α complex may partly reduce the promoting effect of FK506 on HCC.

Gene-Chemical Interaction Annotations    
plerixafor  (EXP,ISO)
tacrolimus (anhydrous)  (EXP,ISO)

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Cxcr4  (C-X-C motif chemokine receptor 4)

Genes (Mus musculus)
Cxcr4  (chemokine (C-X-C motif) receptor 4)

Genes (Homo sapiens)
CXCR4  (C-X-C motif chemokine receptor 4)

Additional Information