Abstract
Context:
Treatment failure due to multidrug resistance (MDR) is a crucial hurdle during chemotherapy. MDR is generally correlated with an upregulation of adenosine triphosphate (ATP)-binding cassette (ABC) transport proteins. Also, aberrant activation of the phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway can counteract chemotherapeutic induction. Identification of safe and functioning MDR-reversing compounds is necessary in gastric-cancer therapy.
Objective:
The study intended to examine the role of Quercetin (Qur) in the mediation of osmotic glycoprotein (P-gp) expression and activity as an ABC transporter in the PI3K/Akt/ P-gp cascade in the oxaliplatin (OxR)-resistant, gastric-cancer cell line KATOIII/OxR.
Design:
The research team performed a laboratory study.
Setting:
The study took place at Nantong Haimen People's Hospital.
Outcome measures:
The research team: (1) determined the impact of OxR on cell viability after treatment with Qur using trypan blue and "3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide" (MTT) assays; (2) employed a rhodamine 123 (Rh123) assay to detect the activity of P-gp; (3) used quantitative reverse transcription polymerase chain reaction (RT-qPCR) to measure mRNA expression of P-gp; and (4) detected apoptosis using an enzyme-linked immunoassay (ELISA) cell-death assay.
Results:
Qur: (1) increased the cytotoxicity of OxR; (2) downregulated the expression level and activity of P-gp and reversed MDR through the enhancement of the cytotoxicity of intracellular OxR in KATOIII/OxR cells; and (3) enhanced the apoptosis rate in KATOIII/OxR cells.
Conclusions:
Qur induced a dramatic reduction in the survival rate of KATOIII/OxR cells and may reverse OxR resistance through a decrease in P-gp expression and activity. These data imply that exposure of KATOIII/OxR cells in the dose-dependent manner to Qur can circumvent MDR by improving the intracellular accumulation of OxR. Qur might provide a new treatment strategy and improve patients' survival after chemotherapy for gastric cancer.
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