STAT3 Decoy Oligodeoxynucleotides-Loaded Solid Lipid Nanoparticles Induce Cell Death and Inhibit Invasion in Ovarian Cancer Cells

• DOI: 10.1371/journal.pone.0124924
• Publication Date: 2015-04-29T18:23:05Z
• Authors: Yanhui Ma; Xiaolei Zhang; Xiaoxuan Xu; Liang Shen; Yao Yao; Ziyan Yang; Peishu Liu
• Keywords: STAT3 Transcription Factor; 0301 basic medicine; Science; Down-Regulation; Apoptosis; Inhibitor of Apoptosis Proteins; 03 medical and health sciences; Microscopy, Electron, Transmission; Cell Movement; Cell Line, Tumor; Autophagy; Humans; Cell Proliferation; Ovarian Neoplasms; Caspase 3; Q; R; Gene Transfer Techniques; Oligonucleotides, Antisense; Cadherins; 3. Good health; Matrix Metalloproteinase 9; Medicine; Nanoparticles; Female; Snail Family Transcription Factors; Research Article; Transcription Factors

Recent advances in the synthesis of multi-functional nanoparticles have opened up tremendous opportunities for the targeted delivery of genes of interest. Cationic solid lipid nanoparticles (SLN) can efficiently bind nucleic acid molecules and transfect genes in vitro. Few reports have combined SLN with therapy using decoy oligodeoxynucleotides (ODN). In the present study, we prepared SLN to encapsulate STAT3 decoy ODN; then, the properties and in vitro behavior of SLN-STAT3 decoy ODN complexes were investigated. SLN-STAT3 decoy ODN complexes were efficiently taken up by human ovarian cancer cells and significantly suppressed cell growth. Blockage of the STAT3 pathway by SLN-STAT3 decoy ODN complexes resulted in an evident induction of cell death, including apoptotic and autophagic death. The mechanism involved the increased expression of cleaved caspase 3, Bax, Beclin-1 and LC3-II and reduced expression of Bcl-2, pro-caspase 3, Survivin, p-Akt and p-mTOR. In addition, SLN-STAT3 decoy ODN complexes inhibited cell invasion by up-regulating E-cadherin expression and down-regulating Snail and MMP-9 expression. These findings confirmed that SLN as STAT3 decoy ODN carriers can induce cell death and inhibit invasion of ovarian cancer cells. We propose that SLN represent a potential approach for targeted gene delivery in cancer therapy.