ZFX knockdown inhibits growth and migration of non-small cell lung carcinoma cell line H1299

Int J Clin Exp Pathol. 2013 Sep 15;6(11):2460-7. eCollection 2013.

Abstract

ZFX (zinc finger transcription factor, X chromosome-linked) contributes to the maintenance of different types of stem cells and the progression of various cancers. We have previously reported that ZFX knockdown inhibits proliferation of glioma in vitro and in vivo. Since overexpression of ZFX in lung cancer tissue correlates with lymph node metastasis, we hypothesized that ZFX may play a role in lung cancer. In this study, we identified ZFX as a promoter of lung cancer growth and migration in a NSCLC (non-small cell lung carcinoma) cell line H1299. ZFX knockdown caused proliferation inhibition determined by MTT assay and colony formation assay, G0/G1 arrest of cell cycle and slightly increased proportion of apoptotic cells assessed by flow cytometry assay, decreased population of migrating cells showed by wound-healing assay, increased cell senescence evidenced by senescence-associated β-galactosidase staining. ZFX knockdown also led to decreased proportion of tumor bearing mice and reduced mean tumor volume in a subcutaneous tumor model. In addition, western blot showed that ZFX knockdown down regulated a set of proteins involved in proliferation, survival and motility. Altogether, these results suggest that ZFX may be a potential therapeutic target for NSCLC.

Keywords: ZFX; growth; migration; non-small cell lung carcinoma; senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Cellular Senescence
  • Gene Knockdown Techniques
  • Genetic Therapy*
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA Interference
  • Time Factors
  • Transfection
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Kruppel-Like Transcription Factors
  • zinc finger protein, X-linked