Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles

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...

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Bibliographic Details
Published in:Oncotarget 2014-08, Vol.5 (15), p.6453-6465
Main Authors: Xiong, Xunhao, Arvizo, Rochelle R, Saha, Sounik, Robertson, David J, McMeekin, Scott, Bhattacharya, Resham, Mukherjee, Priyabrata
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cisplatin - pharmacology
Disease Models, Animal
Down-Regulation
Drug Synergism
Epithelial-Mesenchymal Transition - drug effects
Female
Gold - administration & dosage
Humans
Metal Nanoparticles - administration & dosage
Mice
Mice, Nude
Nanoparticles
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - pathology
Research Paper
Signal Transduction
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.2203