Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer

HongYan Liu, Xiaolin Yu, Haitao Liu, Daqing Wu, Jin-Xiong She

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally "undruggable" targets.

Original languageEnglish (US)
Article number30346
JournalScientific Reports
Volume6
DOIs
StatePublished - Jul 26 2016

Fingerprint

Small Interfering RNA
Prostatic Neoplasms
Nucleotide Aptamers
Antibodies
Heterografts
Vascular Endothelial Growth Factor A
Cause of Death
Neoplasms
Phosphotransferases
Therapeutics
Apoptosis
Growth
human glutamate carboxypeptidase II
In Vitro Techniques

ASJC Scopus subject areas

  • General

Cite this

Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer. / Liu, HongYan; Yu, Xiaolin; Liu, Haitao; Wu, Daqing; She, Jin-Xiong.

In: Scientific Reports, Vol. 6, 30346, 26.07.2016.

Research output: Contribution to journalArticle

@article{b234df921f7b47fea27cd66947688723,
title = "Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer",
abstract = "Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally {"}undruggable{"} targets.",
author = "HongYan Liu and Xiaolin Yu and Haitao Liu and Daqing Wu and Jin-Xiong She",
year = "2016",
month = "7",
day = "26",
doi = "10.1038/srep30346",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer

AU - Liu, HongYan

AU - Yu, Xiaolin

AU - Liu, Haitao

AU - Wu, Daqing

AU - She, Jin-Xiong

PY - 2016/7/26

Y1 - 2016/7/26

N2 - Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally "undruggable" targets.

AB - Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally "undruggable" targets.

UR - http://www.scopus.com/inward/record.url?scp=84979530046&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979530046&partnerID=8YFLogxK

U2 - 10.1038/srep30346

DO - 10.1038/srep30346

M3 - Article

C2 - 27456457

AN - SCOPUS:84979530046

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 30346

ER -