Survivin small interfering RNA transfected with a microbubble and ultrasound exposure inducing apoptosis in ovarian carcinoma cells

Int J Gynecol Cancer. 2010 May;20(4):500-6. doi: 10.1111/IGC.0b013e3181c5ddfa.

Abstract

Introduction: Small interfering RNA (siRNA) has been used to knock down the expression of specific genes. However, its delivery remains a challenge. Recently, ultrasound combined with microbubbles has been used to deliver plasmid into cells and has shown much superiority. Whether a survivin siRNA transfected with a microbubble contrast agent combined with ultrasound exposure could inhibit survivin expression and induce ovarian cancer cell apoptosis was investigated.

Methods: The survivin gene was amplified and inserted into vector pEGFP-N1, resulting in psurvivin-EGFP. Three siRNA expression cassettes (SECs) targeting survivin were obtained by 2-step polymerase chain reaction. The SECs and psurvivin-EGFP were cotransfected into 293T cells. A functional SEC was selected and inserted into pMD18T, resulting in the survivin-targeting siRNA expression plasmid, which was transfected into SKOV-3 ovarian carcinoma cells using SonoVue, a microbubble contrast agent, and ultrasound exposure. Survivin expression was monitored by Western blot, and apoptosis was determined by fluorescence-activated cell sorting.

Results: One siRNA effectively inhibited survivin expression. SonoVue with ultrasound effectively delivered survivin siRNA to SKOV-3 cells, inhibited survivin expression, and induced apoptosis.

Conclusions: Delivery of survivin siRNA using a microbubble contrast agent combined with ultrasound exposure can effectively inhibit survivin expression and induce apoptosis, providing a new promising approach for siRNA delivery in vivo.

MeSH terms

  • Apoptosis*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microbubbles*
  • Microtubule-Associated Proteins / antagonists & inhibitors
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Transfection
  • Ultrasonics*

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Survivin