N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells. Cancer Lett

Asian Liver Center, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5655, USA.
Cancer letters (Impact Factor: 5.62). 02/2008; 262(1):133-42. DOI: 10.1016/j.canlet.2007.12.010
Source: PubMed


The over-expression of N-myc down-regulated gene 1 (NDRG1) in hepatocellular carcinoma (HCC) was previously reported to correlate with vascular invasion and patient survival. Our current study aims to elucidate its functions in HCC. We found that it lacked the tumorigenic ability to promote soft agar colony formation or serum-independent growth of NIH3T3 cells. We used specific small interfering RNA (siRNA) oligos to suppress the expression of NDRG1 in human HCC (Hep3B and HepG2) cell lines, and found that this significantly reduced cell proliferation and invasion, and induced apoptosis. Additionally, NDRG1-specific siRNA inhibited the HepG2 xenograft growth in nude mice. These results are consistent with our earlier clinical observations that NDRG1 is associated with more aggressive tumor behavior, and suggest that NDRG1 may be a potential therapeutic target for HCC.

3 Reads
  • Source
    • "The downregulation of NDRG1 in vitro has been found to inhibit cell migration and invasion (13,28). These findings indicate that NDRG1 has potential oncogenic properties in hepatocarcinogenesis and that it contributes to HCC progression, including vascular invasion and intrahepatic metastasis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: N-myc downstream-regulated gene 1 (NDRG1) has been reported to be a multifunctional protein associated with carcinogenesis and tumor progression. However, the cellular function of NDRG1 remains elusive in human hepatocellular carcinoma (HCC). No NDRG1 expression is observed in normal liver tissue. Overexpression of NDRG1 has been observed in human HCC, particularly with aggressive invasion, metastasis, poor differentiation and short patient survival. In addition, recent studies have shown that NDRG1 exhibits an inhibitory effect on HCC growth in vitro and in vivo, which contrasts with previous reports indicating that NDRG1 promotes the proliferation and invasion of HCC cell lines. Further studies have shown that the localization of NDRG1 is variable, translocating to the nucleus or membrane according to the cell state, which may relate to the diverse function of NDRG1. The present study reviews our current knowledge with regard to the functions of NDRG1 in HCC and other types of human cancer.
    Oncology letters 12/2013; 6(6):1539-1542. DOI:10.3892/ol.2013.1636 · 1.55 Impact Factor
  • Source
    • "We and others have found that aberrant expression of a novel metastasis suppressor, N-myc downregulated gene 1 (NDRG1), was involved in the process of CRC development [9]–[12]. NDRG1 exerts its function through modulating the major signaling pathways in a large variety of tumor types including CRC [9], [10], [13]–[15]. Nevertheless, the association of NDRG1 with cancer progression has been reported with inconsistent observations. For instance, NDRG1 expression in breast, liver, lung and cervical cancers was positively correlated to the disease relapse and was a poor prognostic indicator for the patient survival [16]–[20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Metastasis remains to be one of the most prevalent causes leading to poor long-term survival of colorectal cancer (CRC) patients. The clinical significances of tumor metastatic suppressor, N-myc downregulated gene 1 (NDRG1), have been inconsistently reported in a variety of cancerous diseases. In this study with 240 CRC clinical specimens, we showed that NDRG1 expression was significantly decreased in most of CRC tissues compared to the paired non-tumor counterparts. Statistical analysis revealed a significant inverse correlation of NDRG1 expression with tumor stage, differentiation status and metastasis. Compared with NDRG1-negative group, NDRG1-positve group had better disease-free/overall survival (p = 0.000) over 5 years' follow-up. Furthermore, NDRG1 was considered to be an independent prognostic factor for overall survival (p = 0.001) and recurrence (p = 0.003). Our study concludes that NDRG1 is a novel favorable predictor for the prognosis in CRC patients.
    PLoS ONE 07/2013; 8(7):e68206. DOI:10.1371/journal.pone.0068206 · 3.23 Impact Factor
  • Source
    • "Moreover, NDRG1 expression is associated with a more aggressive tumor phenotype and poor outcome in colorectal cancer [11]. NDRG1 mediates apoptosis in several tissues [8] [12] [13]. However, the regulation of NDRG1 during apoptosis state in cancer cells in general, and in colon cancer in particular, was not explored previously. "
    [Show abstract] [Hide abstract]
    ABSTRACT: N-myc downstream regulated gene-1 participates in carcinogenesis, angiogenesis, metastases, and anticancer drug resistance. In the present study, we analyzed the expression pattern of N-myc downstream regulated gene-1 following treatment of human colonic cancer cell lines; HCT-116 (well differentiated with wild-type p53 gene) and Colo-320 (poorly differentiated with mutant p53 gene), with 3,3'-diindolylmethane, a well-established proapoptotic agent product derived from indole-3-carbinol. Treatment of Colo-320 and HCT-116 with 3,3'-diindolylmethane disclosed inhibition of cell viability in a dose-dependent manner, mediated through apoptosis induction. The increased expression of N-myc downstream regulated gene-1 was detected only in poorly differentiated colon cancer cells, Colo-320 cell line. Our results suggest that N-myc downstream regulated gene-1 expression is enhanced by 3,3'-diindolylmethane in poorly differentiated cells and followed by induction of apoptosis. 3,3'-diindolylmethane induced apoptosis may represent a new regulator of N-myc downstream regulated gene-1 in poorly differentiated colonic cancer cells.
    BioMed Research International 01/2012; 2012:256178. DOI:10.1155/2012/256178 · 2.71 Impact Factor
Show more