Lentivirus-mediated shRNA interference targeting SLUG inhibits lung cancer growth and metastasis

Asian Pac J Cancer Prev. 2012;13(10):4947-51. doi: 10.7314/apjcp.2012.13.10.4947.

Abstract

Objective: Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer.

Methods: We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods.

Results: Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin.

Conclusion: These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation*
  • Humans
  • Immunoenzyme Techniques
  • Lentivirus / genetics*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • SNAI1 protein, human
  • SNAI2 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors