Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles
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Xunhao Xiong1,*, Rochelle R. Arvizo2,*, Sounik Saha1, David J. Robertson3, Scott McMeekin4,5, Resham Bhattacharya4,5 and Priyabrata Mukherjee5
1 Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
2 Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN
3 Department of Chemistry and University of Missouri Research Reactor, University of Missouri, Columbia, Missouri
4 Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
5 Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
* These authors contributed equally to this work
Priyabrata Mukherjee, email:
Keywords: gold nanoparticle; chemoresistance; cancer stem cell; EMT; NF-kappa B
Received: May 22, 2014 Accepted: July 11, 2014 Published: July 11, 2014
Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth and metastasis in mice by reversing epithelial-mesenchymal transition (EMT). Since EMT is known to confer drug resistance to cancer cells, we wanted to investigate whether anti-EMT property of AuNP could be utilized to sensitize ovarian cancer cells to cisplatin. Herein, we report that AuNPs prevent cisplatin-induced acquired chemoresistance and stemness in ovarian cancer cells and sensitize them to cisplatin. AuNPs inhibit cisplatin induced EMT, decrease the side population cells and key stem cell markers such as ALDH1, CD44, CD133, Sox2, MDR1 and ABCG2 in ovarian cancer cells. Mechanistically, AuNPs prevent cisplatin-induced activation of Akt and NF-kB signaling axis in ovarian cancer cells that are critical for EMT, stem cell maintenance and drug resistance. In vivo, AuNPs sensitize orthotopically implanted ovarian tumor to a low dose of cisplatin and significantly inhibit tumor growth via facilitated delivery of both AuNP and cisplatin. These findings suggest that by depleting stem cell pools and inhibiting key molecular pathways gold nanoparticles sensitize ovarian cancer cells to cisplatin and may be used in combination to inhibit tumor growth and metastasis in ovarian cancer.
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