Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications

  • Authors:
    • Xuyu Yang
    • Xiaoling Zhou
    • Paul Tone
    • Marian E. Durkin
    • Nicholas C. Popescu
  • View Affiliations

  • Published online on: June 24, 2016     https://doi.org/10.3892/ol.2016.4781
  • Pages: 1591-1596
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Abstract

Human hepatocellular carcinoma (HCC) is one of the most common types of cancer and has a very poor prognosis; thus, the development of effective therapies for the treatment of advanced HCC is of high clinical priority. In the present study, the anti‑oncogenic effect of combined knockdown of c‑Myc expression and ectopic restoration of deleted in liver cancer 1 (DLC1) expression was investigated in human liver cancer cells. Expression of c‑Myc in human HCC cells was knocked down by stable transfection with a Myc‑specific short hairpin (sh) RNA vector. DLC1 expression in Huh7 cells was restored by adenovirus transduction, and the effects of DLC1 expression and c‑Myc knockdown on Ras homolog gene family, member A (RhoA) levels, cell proliferation, soft agar colony formation and cell invasion were measured. Downregulation of c‑Myc or re‑expression of DLC1 led to a marked reduction in RhoA levels, which was associated with decreases in cell proliferation, soft agar colony formation and invasiveness; this inhibitory effect was augmented with a combination of DLC1 transduction and c‑Myc suppression. To determine whether liver cell‑specific delivery of DLC1 was able to enhance the inhibitory effect of c‑Myc knockdown on tumor growth in vivo, DLC1 vector DNA complexed with galactosylated polyethylene glycol‑linear polyethyleneimine was administered by tail vein injection to mice bearing subcutaneous xenografts of Huh7 cells transfected with shMyc or control shRNA. A cooperative inhibitory effect of DLC1 expression and c‑Myc knockdown on the growth of Huh7‑derived tumors was observed, suggesting that targeted liver cell delivery of DLC1 and c‑Myc shRNA may serve as a possible gene therapy modality for the treatment of human HCC.
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August-2016
Volume 12 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Yang X, Zhou X, Tone P, Durkin ME and Popescu NC: Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications. Oncol Lett 12: 1591-1596, 2016
APA
Yang, X., Zhou, X., Tone, P., Durkin, M.E., & Popescu, N.C. (2016). Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications. Oncology Letters, 12, 1591-1596. https://doi.org/10.3892/ol.2016.4781
MLA
Yang, X., Zhou, X., Tone, P., Durkin, M. E., Popescu, N. C."Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications". Oncology Letters 12.2 (2016): 1591-1596.
Chicago
Yang, X., Zhou, X., Tone, P., Durkin, M. E., Popescu, N. C."Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications". Oncology Letters 12, no. 2 (2016): 1591-1596. https://doi.org/10.3892/ol.2016.4781