STAT3 Decoy Oligodeoxynucleotides-Loaded Solid Lipid Nanoparticles Induce Cell Death and Inhibit Invasion in Ovarian Cancer Cells.
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.
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Yanhui
Y
Ma
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Xiaolei
X
Zhang
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Xiaoxuan
X
Xu
Department of Obstetrics and Gynecology, Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, China.
Liang
L
Shen
Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
Yao
Y
Yao
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Ziyan
Z
Yang
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Peishu
P
Liu
D017209:Apoptosis; D001343:Autophagy; D015820:Cadherins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
D015820:Cadherins; D051034:Inhibitor of Apoptosis Proteins; D016376:Oligonucleotides, Antisense; D050796:STAT3 Transcription Factor; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9