ABSTRACT
Aim To screen the differential microRNA (miRNA) expression profiles of different metastatic po-tential liver cancer cell lines,and predict miRNAs-reg-ulated target genes and their functions. Methods To-tal RNA was extracted and the miRNA expression pro-files were obtained by miRNA microarray chip hybrid-ization. The miRNAs whose expression had significant difference were selected by analyzing the miRNA difference expression profiles of the two different meta-static potential liver cancer cell lines, namely MHCC-97H(high-metastasis) and Hep3B(non-metastasis), which were compared with normal hepatocytes L02 re-spectively. Moreover, we analyzed the miRNA differ-ential expression profile between liver cancer cell lines MHCC-97H and Hep3B. The miRNAs were verified by qPCR and target genes were predicted by four softwares (TargetScan, miRanda, miRWalk, miRDB). To un-derstand the biological functions of predicted target genes, bioinformatics analysis was performed. Results The miRNA microarray results showed that the ex-pression of miR-192-5p and miR-215-5p significantly increased in liver cancer cell lines (MHCC-97H, Hep3B) when compared with normal hepatocytes L02, while miR-130a-3p and miR-196a-5p were significantly reduced; compared with Hep3B, the expression of miR-224-5p markedly increased in liver cancer cell line MHCC-97H, while miR-146a-5p, miR-483-3p and miR-200b-3p were significantly reduced. The re-sults of qRT-PCR were consistent with chip results. Conclusion There are differences of miRNA expres-sion profiles in different metastatic potential liver canc-er cell lines MHCC-97H, Hep3B, and they may par-ticipate in regulating the development and invasion of hepatocellular carcinoma.
ABSTRACT
Objective To study manganese superoxide dismutase (MnSOD) expression in colorectal cancer (CRC) cells and observe its relation to metastatic potential. To investigate the diagnostic performance of manganese-enhanced magnetic resonance imaging (MEMRI) for detecting metastatic potential of CRC. Methods High and low metastatic potential CRC cell lines SW620, HCT116, LoVo and SW480, DLD-1, HCT15, Caco-2, as well as normal colon mucosal cell CCD841 CoN were cultured. MnSOD expression level in cells was detected by western blot and the measurement was repeated for three times. HCT15, DLD-1, LoVo and SW620 cells were selected to perform in vitro MEMRI and subcutaneous xenografts were developed for subsequent in vivo MEMRI. MnCl2·4H2O solution was utilized as the contrast agent and T1 shortening was calculated. The differences of MnSOD expression level in cells, average T1 value shortening of cells and xenografts were separately compared by one-way ANOVA.Results The difference of MnSOD expression level in CRC cells were significant (P0.05). Conclusions MEMRI has the potential to noninvasively distinguish different metastatic potential CRC by revealing greater T 1 value shortening in more aggressive one. However the MnSOD expression in CRC cells is not corresponding to malignant potential.
ABSTRACT
PURPOSE: We determined the therapeutic effects of blockade of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor (orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. RESULTS: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators (pMAPK and pAkt), decreased proliferative index, decreased microvessel density (MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. CONCLUSION: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.
Subject(s)
Animals , Mice , Apoptosis , Carcinoma, Squamous Cell , Down-Regulation , Endothelial Cells , Epidermal Growth Factor , Mice, Nude , Microvessels , Mouth Floor , Paclitaxel , Phosphotransferases , Protein-Tyrosine Kinases , Purines , ErbB Receptors , Receptors, Vascular Endothelial Growth Factor , Transplantation, Heterologous , Tyrosine , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2ABSTRACT
Purpose:To study the molecular mechanism that d etermines the cell cycle differences between human giant-cell carcinoma cell st rains 95C and 95D. Methods:FACscan was used to analyze the cell cycle of 95C and 9 5D cells, and the proliferation ability of 95C and 95D cells was measured by MTT assay. We further detected the expression levels of cell cycle factors by Weste rn blotting. Results:Our data showed that the proliferation ability of 95D c ells is higher than that of 95C cells, and that the cell number in S phase of 95 D cells is much larger than that of 95C cells. We further found that the express ion level of p27 in 95D cell is lower than that of 95C cells. In addition, the e xpression levels of CDK2 and p-RB of 95D cells are higher than that of 95C cell s. Conclusions:Our results indicated that low expression level of p27 lead to the increased proliferation ability of 95D cells, which might reflec t the progression of human lung cancer cells in cell cycle facets.