Small interference RNA targeting Krüppel-like factor 8 inhibits the renal carcinoma 786-0 cells growth in vitro and in vivo

J Cancer Res Clin Oncol. 2010 Aug;136(8):1255-65. doi: 10.1007/s00432-010-0776-0. Epub 2010 Feb 25.

Abstract

Purpose: Krüppel-like factor 8 (KLF8) plays an important role in oncogenic transformation and is highly overexpressed in several types of human cancer. We investigated the expression of KLF8 in renal cell carcinoma (RCC) tissues and the role of small interference RNA targeting KLF8 on growth, cell cycle, and apoptosis of human renal carcinoma cell line 786-0 in vitro and in vivo.

Methods: The expression of KLF8 protein and mRNA in human renal carcinoma samples was detected by immunochemistry and reverse transcription polymerase chain reaction (RT-PCR). The effects of small interference RNA (siRNA) targeting KLF8 on growth, invasiveness, cell cycle, and apoptosis of 786-0 cells were evaluated by MTT assay, Matrigel Invasion Assay, and flow cytometry in vitro. We also investigated effect of siRNA targeting KLF8 on growth of 786-0 cells in nude mice in vivo.

Results: Immunohistochemistry and RT-PCR results showed the expression of KLF8 protein and mRNA in RCC specimens was significantly higher than that in the adjacent non-tumorous renal tissues (P < 0.001). KLF8-siRNA depressed the cellular growth and invasion of 786-0 cells in vitro. The flow cytometry results revealed that KLF8-siRNA could induce an increase in G0/G1 phase cells and induce cell apoptosis. Intratumor injection of siRNA targeting KLF8 inhibited the growth of 786-0 cells in vivo in nude mice tumor model.

Conclusions: KLF8 possibly involved in regulating the cell growth, invasion, apoptosis, and proliferation of renal carcinoma cancer cells. Blocking the KLF8 channel might be a potential therapeutic strategy for RCC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Base Sequence
  • Biomarkers, Tumor / genetics
  • Cell Division
  • Cell Line, Tumor
  • DNA Primers
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics*
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • Biomarkers, Tumor
  • DNA Primers
  • KLF8 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Repressor Proteins