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

Ma Y, Zhang X, Xu X, Shen L, Yao Y, Yang Z, Liu P - PLoS ONE (2015)

Bottom Line: 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.We propose that SLN represent a potential approach for targeted gene delivery in cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

SLN-STAT3 decoy ODN complexes induce apoptosis of ovarian cancer cells.(A) SLN-decoy ODN induced a significant increase in apoptosis in SKOV3 and A2780 cells. After 48 hours of transfection, cell apoptosis was detected by annexin V-FITC/PI double-staining assay with flow cytometry. (B) Western blot assays showed that SLN-decoy ODN led to distinct up-regulation of Bax and cleaved caspase 3 and down-regulation of Bcl-2, pro-caspase 3 and Survivin. The data are expressed as the means ± SD of three independent experiments, ** P < 0.01 compared with NC.
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pone.0124924.g004: SLN-STAT3 decoy ODN complexes induce apoptosis of ovarian cancer cells.(A) SLN-decoy ODN induced a significant increase in apoptosis in SKOV3 and A2780 cells. After 48 hours of transfection, cell apoptosis was detected by annexin V-FITC/PI double-staining assay with flow cytometry. (B) Western blot assays showed that SLN-decoy ODN led to distinct up-regulation of Bax and cleaved caspase 3 and down-regulation of Bcl-2, pro-caspase 3 and Survivin. The data are expressed as the means ± SD of three independent experiments, ** P < 0.01 compared with NC.

Mentions: To investigate the effect of the SLN-decoy ODN on cell apoptosis, the apoptotic rate was quantified through annexin V-FITC and PI double staining. Compared with those of the control groups, the apoptotic rates of the SLN-decoy ODN complexes (SKOV3 20.74%; A2780 24.64%) and Lipo-decoy ODN (SKOV3 21.59%; A2780 22.41%) were notably higher (P < 0.01; Fig 4A). These findings indicated that the SLN-decoy ODN complexes could affect the apoptotic program. The data also suggested that the apoptosis induction effect of SLN-decoy ODN was not due to the nanoparticle carrier because the SLN did not increase the apoptotic rate. To further explore the potential molecular mechanisms by which the SLN-decoy ODN complexes induce cell apoptosis, apoptosis-related proteins were detected by Western blot assays (Fig 4B). The results showed that the expression of Bax and cleaved caspase 3 were significantly increased in the SLN-decoy ODN and Lipo-decoy ODN groups. Furthermore, the protein levels of Bcl-2, pro-caspase 3 and Survivin were markedly reduced in the two abovementioned groups in both SKOV3 and A2780 cells.


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

Ma Y, Zhang X, Xu X, Shen L, Yao Y, Yang Z, Liu P - PLoS ONE (2015)

SLN-STAT3 decoy ODN complexes induce apoptosis of ovarian cancer cells.(A) SLN-decoy ODN induced a significant increase in apoptosis in SKOV3 and A2780 cells. After 48 hours of transfection, cell apoptosis was detected by annexin V-FITC/PI double-staining assay with flow cytometry. (B) Western blot assays showed that SLN-decoy ODN led to distinct up-regulation of Bax and cleaved caspase 3 and down-regulation of Bcl-2, pro-caspase 3 and Survivin. The data are expressed as the means ± SD of three independent experiments, ** P < 0.01 compared with NC.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4414561&req=5

pone.0124924.g004: SLN-STAT3 decoy ODN complexes induce apoptosis of ovarian cancer cells.(A) SLN-decoy ODN induced a significant increase in apoptosis in SKOV3 and A2780 cells. After 48 hours of transfection, cell apoptosis was detected by annexin V-FITC/PI double-staining assay with flow cytometry. (B) Western blot assays showed that SLN-decoy ODN led to distinct up-regulation of Bax and cleaved caspase 3 and down-regulation of Bcl-2, pro-caspase 3 and Survivin. The data are expressed as the means ± SD of three independent experiments, ** P < 0.01 compared with NC.
Mentions: To investigate the effect of the SLN-decoy ODN on cell apoptosis, the apoptotic rate was quantified through annexin V-FITC and PI double staining. Compared with those of the control groups, the apoptotic rates of the SLN-decoy ODN complexes (SKOV3 20.74%; A2780 24.64%) and Lipo-decoy ODN (SKOV3 21.59%; A2780 22.41%) were notably higher (P < 0.01; Fig 4A). These findings indicated that the SLN-decoy ODN complexes could affect the apoptotic program. The data also suggested that the apoptosis induction effect of SLN-decoy ODN was not due to the nanoparticle carrier because the SLN did not increase the apoptotic rate. To further explore the potential molecular mechanisms by which the SLN-decoy ODN complexes induce cell apoptosis, apoptosis-related proteins were detected by Western blot assays (Fig 4B). The results showed that the expression of Bax and cleaved caspase 3 were significantly increased in the SLN-decoy ODN and Lipo-decoy ODN groups. Furthermore, the protein levels of Bcl-2, pro-caspase 3 and Survivin were markedly reduced in the two abovementioned groups in both SKOV3 and A2780 cells.

Bottom Line: 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.We propose that SLN represent a potential approach for targeted gene delivery in cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus