Knockdown of Eag1 Expression by RNA Interference Increases Chemosensitivity to Cisplatin in Ovarian Cancer Cells

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2015-12, Vol.22 (12), p.1618-1626
• Main Authors: Hui, Chen, Lan, Zhang, Yue-li, Lin, Li-lin, Hong, Li-lin, Huang
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; ATP Binding Cassette Transporter, Sub-Family B - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cisplatin - pharmacology; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm - genetics; Embryology; Ether-A-Go-Go Potassium Channels - genetics; Ether-A-Go-Go Potassium Channels - metabolism; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Inhibitory Concentration 50; Kaplan-Meier Estimate; Medicine & Public Health; Middle Aged; Multidrug Resistance-Associated Proteins; NF-kappa B - metabolism; Obstetrics/Perinatology/Midwifery; Original Article; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Reproductive Medicine; RNA Interference; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction - drug effects; Time Factors; Transfection
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1177/1933719115590665

Ether á go-go 1 (Eag1) is frequently highly expressed in various malignant cancers and its excessive expression is correlated with poor prognosis in various cancers. However, the relationship of Eag1 expression with the clinical outcome of patients having ovarian cancer treated with cisplatin-based adjuvant chemotherapy is still unknown. In this study, we measured the expression of Eag1 in ovarian cancer and investigated the association between cisplatin chemosensitivity of ovarian cancer cells and Eag1 expression level. We demonstrate that decreased expression of Eag1 correlates with favorable prognosis in patients treated with cisplatin-based adjuvant chemotherapy and predicts higher cisplatin sensitivity in ovarian cancer cells. In vitro, knockdown of Eag1 by small interfering RNA facilitated the sensitivity of ovarian cancer cells (SKOV3 and TYK) to cisplatin-induced apoptosis via nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) pathway. Furthermore, knockdown of Eag1 expression was associated with decreased expression of the P-glycoprotein without affecting multidrug resistance-associated protein 1 expression. Taken together, Eag1 may serve as a potential indicator to predict Eag1 chemosensitivity, and silencing Eag1 may represent a potential therapeutic strategy for ovarian cancer.