Investigation effects of ATRA as an antineoplastic agent in OVCAR-3 cells

Ovarian cancer which is the most common types of gynecological cancer has a high percentage at the rate of death due to cancer in women. Depending on the number of diagnosis and rates of death, it is thought that ovarian cancer continues to be the most lethal gynecological malignancy.Retinoids, which are natural and synthetic vitamin A derivatives, are the hydrophobic components. They play an active role in cell differentiation, cell proliferation, homeostasis, and development. They inhibit the uncontrolled cellular proliferation in cancer cells, lead to cell differentiation and induce apoptosis in cells. ATRA (All-Trans Retinoic Acid) is a physiological metabolite. They play an active role in expression of target genes by binding to nuclear receptors. Retinoic acid derivatives inhibit the growth of ovarian cancer cells both in vivo and cell culture studies.In this thesis, it is studied the effects of the metabolite of retinol ATRA alone and in combination with conventional chemotherapeutics which are carboplatin and paclitaxel on OVCAR-3 (human ovarian epithelial adenocarcinoma cell line) cell line. For this purpose, MTT (3-(4,5 dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) method for determination of cytotoxic effects, caspase-3 enzyme activity and DAPI (4-6 diamidino-phenylindole) dying for the assessment of apoptosis were applied. Changes in gene expression levels of VEGF, COX-2, IRS-1 and Ki-67 genes has determined with applying real-time quantitative polymerase chain reaction (RT-PCR) technique.Depending on the dose and time, applying ATRA alone causes cytotoxic effects, inducing apoptosis, decreased gene expression levels of IRS-1 and COX-2 genes in OVCAR-3 cell line. Applying carboplatin and paclitaxel in double and triple combination with ATRA in OVCAR-3 cell line effects on the cells in a shorter time with respect to the application ATRA alone.Keywords: Antineoplastic, ATRA, MTT, DAPI, Caspase-3, RT-PCR.