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Alteration of protein and gene expressions of Hexokinase II in PC3 cell lines by cisplatinmetformin combination treatment

Durukan, Özlem
Akkulak, Merve
Evin, Emre
Arslan, Şevki
Adalı, Orhan
Metformin is an antidiabetic drug with anticancer properties. Cisplatin is known as one of the most potent chemotherapeutics for treatment of various types of cancer. In order to overcome cisplatin resistance and toxicity, the drug can be combined with other drugs that sensitize tumour cells to cisplatin. The ability of metformin to potentiate cisplatin-mediated killing of cancer cells in vitro, makes it a plausible candidate for combination with cisplatin- based therapy. The aim of this study is to examine the combined effect of these drugs on protein and mRNA expressions of Hexokinase II, a regulatory enzyme participating in glycolysis as well as cancer promotion. The effects of drugs on prostate cancer cell lines were studied using androgen independent PC3 cell line. Cells were treated with either metformin alone in the range of 1–10 mM, cisplatin alone or a combination of these two drugs. Cytotoxicity of drugs were determined with Alamar Blue Assay and IC50 was calculated. The effects of drugs on Hexokinase II mRNA and protein expressions were determined by qRT-PCR and western immunoblotting techniques, respectively. The intensity of each band was analyzed by Image J software program. IC50 value of cisplatin on PC3 cell line was found as 30 lM. Both alone or combination of drugs were inhibited the proliferation of PC3 cells in a concentration dependent manner. Hexokinase II mRNA and protein expressions were significantly downregulated in metformin/cisplatin treated cells compared to control groups. Epidemiological and experimental researches indicates that men with abdominal obesity is a risk factor for prostate cancer. Parallel with our results, the adjuvant role of this type of antidiabetic drug must be investigated for new cancer treatment options.