In�vitro study on reversal of ovarian cancer cell resistance to cisplatin by naringin via the nuclear factor-κB signaling pathway

Abstract

Abstract. 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)-κB and P-glycoprotein (P-gp) in the SKOV3/CDDP cell line. Small interfering RNA (siRNA) targeting NF-κB was designed and synthesized to silence NF-κB, and recombinant plasmid vectors overexpressing NF-κB were constructed to transfect cells. RT-qPCR and western blotting assays were subsequently performed to detect the effects of NF-κB on the expression of P-gp at the mRNA and protein levels. Naringin was added to the NF-κB-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-κB and P-gp were significantly decreased in a dose-dependent manner by naringin treatment (P<0.05). In cells overexpressing NF-κB, P-gp expression was significantly elevated (P<0.05), and the expression of P-gp was significantly decreased when NF-κB was silenced (P<0.05). Treatment with naringin was able to significantly ameliorate the NF-κB-induced overexpression of P-gp (P<0.05). These results indicate that naringin is able to inhibit the expression of NF-κB and P-gp in SKOV3/CDDP cells. Such an inhibitory effect may increase gradually with concentration, and is associated with blockade of the NF-κB 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.

A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies

“…NF-κB is highly expressed in cisplatin-resistant ovarian cancer cell lines and has a crucial role in the drug resistance of ovarian cancer cells ( Choi et al, 2008 ). One study demonstrated that the inhibitory effect of naringin was associated with inhibition of the NF-κB signaling pathway, and treatment with naringin significantly reduced P-glycoprotein (P-gp) and NF-κB expression in a concentration-dependent way in SKOV3/CDDP cisplatin-resistant human epithelial ovarian cancer cell line ( Zhu et al, 2018 ). Another study also indicated that naringin downregulated COX-2 and NF-κB expression in a concentration-dependent way in SKOV3/CDDP cells ( Zhu et al, 2017 ).…”

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

“…A few flavonoids, including naringin (Zhu et al, 2018) and taxifolin (Chen et al, 2018), have been identified as substrates of P-gp. The cellular uptake of 40 flavonoids was measured in parental human mouth epidermal carcinoma (KB) cells and KB/MDR cells with or without elacridar.…”

Effects of naringin on reversing cisplatin resistance and the Wnt/β-catenin pathway in human ovarian cancer SKOV3/CDDP cells

“…The mechanism of this activity may be related to regulation of the NF-κB signaling pathway. 6 In this study, we found that different concentrations of naringin inhibited the proliferation of SKOV3/CDDP cells in a time- and dose-dependent manner. After 20 µmol/L naringin treatment of SKOV3/CDDP-CN for 48 hours, the inhibition rate increased with increasing cisplatin concentrations compared with the 0-µmol/L naringin group (P < 0.05).…”

“…The reversal mechanism might be associated with the NF-κB pathway. 6 However, the exact mechanism of naringin in ovarian cancer cells remains largely unknown.…”