In vitro study on reversal of ovarian cancer cell resistance to cisplatin by naringin via the nuclear factor-[kappa]B signaling pathway

• Published in: Experimental and therapeutic medicine Vol. 15; no. 3; p. 2643
• Main Authors: Zhu, Hong, Gao, Jun, Wang, Lei, Qian, Ke-Jian, Cai, Li-Ping
• Format: Journal Article
• Language: English
• Published: Spandidos Publications 01.03.2018
• Subjects: Care and treatment; Development and progression; Drug resistance; Gene expression; Genetic aspects; Glycosides; Health aspects; Ovarian cancer; Oxaliplatin; Patient outcomes; Prevention; Transcription factors
• ISSN: 1792-0981
• DOI: 10.3892/etm.2018.5695

The aim of the present study was to investigate the mechanism of action by which naringin reverses the resistance of ovarian cancer cells to cisplatin. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting assays were used to detect the effects of different concentrations of naringin on the expressions of nuclear factor (NF)-[kappa]B and P-glycoprotein (P-gp) in the SKOV3/CDDP cell line. Small interfering RNA (siRNA) targeting NF-[kappa]B was designed and synthesized to silence NF-[kappa]B, and recombinant plasmid vectors overexpressing NF-[kappa]B were constructed to transfect cells. RT-qPCR and western blotting assays were subsequently performed to detect the effects of NF-[kappa]B on the expression of P-gp at the mRNA and protein levels. Naringin was added to the NF-[kappa]B-overexpressing SKOV3/CDDP cells and cultured for 48 h, followed by the detection of the expression of P-gp. RT-PCR and western blotting results demonstrated that the gene and protein expressions of NF-[kappa]B and P-gp were significantly decreased in a dose-dependent manner by naringin treatment (P<0.05). In cells overexpressing NF-[kappa]B, P-gp expression was significantly elevated (P<0.05), and the expression of P-gp was significantly decreased when NF-[kappa]B was silenced (P<0.05). Treatment with naringin was able to significantly ameliorate the NF-[kappa]B-induced overexpression of P-gp (P<0.05). These results indicate that naringin is able to inhibit the expression of NF-[kappa]B and P-gp in SKOV3/CDDP cells. Such an inhibitory effect may increase gradually with concentration, and is associated with blockade of the NF-[kappa]B signaling pathway. This pathway may represent one of the mechanisms of action by which Naringin reverses resistance to platinum-based agents in ovarian cancer cells. Key words: ovarian cancer, naringin, SKOV3/CDDP cell line, resistance, cisplatin, nuclear factor-[kappa]B signaling pathway