Publications (2)5.88 Total impact
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Article: Zinc finger E-box binding homeobox 1 promotes invasion and bone metastasis of small cell lung cancer in vitro and in vivo.
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ABSTRACT: Bone is one of the most frequent targets of small cell lung cancer (SCLC) metastasis and is closely associated with a poor prognosis, but the specific cellular gene alterations responsible for SCLC with bone metastasis are unclear. Zinc finger E-box binding homeobox 1 (ZEB1) as an E-box transcriptional repressor has been suggested that an important inducer of the epithelial-mesenchymal transition (EMT) and a promoter of tumor metastasis in colon, breast and lung cancers. However, the relationship between ZEB1 and SCLC with bone metastasis is unclear. In this study, ZEB1 was found to be highly expressed in bone-metastatic SCLC tissues and cell lines as compared with those that were non-metastatic (P < 0.05). Using a lentivirus RNA interference technique to knockdown ZEB1 expression in bone-metastatic SCLC cells (SBC-5 cell line), we found that ZEB1 siRNA could inhibit the invasive and migratory ability and decrease parathyroid hormone-related protein expression, as determined by invasion assays and enzyme-linked immunosorbent assays. Besides, ZEB1 siRNA significantly inhibited the bone metastasis of SBC-5 cells in vivo. Furthermore, overexpression of ZEB1 in SBC-3 cells, which demonstrate promoted bone-metastatic potential, dramatically promoted their invasive and migratory ability and parathyroid hormone-related protein expression as well as increased the number and sites of bone metastases in vivo compare to the control group. We also found that SBC-3 cells underwent EMT, as indicated by decreased epithelial markers and increased mesenchymal marker expression. Taken together, these results indicate that ZEB1 promoted the invasive ability and bone metastasis of SCLC cells, and that this was partially mediated via the EMT pathway.Cancer Science 05/2012; 103(8):1420-8. · 3.33 Impact Factor -
Article: Lentivirus-delivered ZEB-1 small interfering RNA inhibits lung adenocarcinoma cell growth in vitro and in vivo.
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ABSTRACT: To explore the relationship between the expression of ZEB1 gene and the proliferation ability of lung adenocarcinoma cells. Immunohistochemistry, Western blot and Real-time PCR were used to detect the expression of ZEB1 gene in lung adenocarcinoma tissue and cell lines compared with adjacent noncancerous region and the human lung fibroblast cell HLF cells. The lentivirus RNA interference technique was used to knock down the expression of ZEB1 in lung adenocarcinoma A549 and H1299 cell lines. Cell cycle and cell apoptosis were measured by FCM assay. In vivo, four groups of 4-week-old nude mice were subcutaneously injected with the stably transfected (ZEB-si, scr-si) cells at a single site to investigate the effect of ZEB1-siRNA in the nude mice tumor growth. In situ apoptosis was detection by TUNEL assay. ZEB-1 was highly expressed in lung adenocarcinoma tissue and cell lines compared with adjacent noncancerous region and the human lung fibroblast cell HLF cells. ZEB1-siRNA could decrease lung adenocarcinoma cell proliferation by delaying S-phase entry and induce cell apoptosis, which led to the inhibition of the tumorigenicity of A549 and H1299 cell lines. Further investigation showed that injecting the ZEB1-siRNA cells into the nude mice could significantly decrease the tumor growth. Knockdown of ZEB-1 expression by lentivirus-delivered siRNA may provide a novel therapeutic target for the treatment of lung cancer.Journal of Cancer Research and Clinical Oncology 04/2012; 138(8):1329-38. · 2.56 Impact Factor
