Abstract
OBJECTIVES:The objectives of this study were to determine the sensitivity of ovarian cancer (OC) cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL (rhTRAIL), and to evaluate the expression profile of TNFRSF10B, TNFRSF10C, TP53TG5, MDM2, BAX, BCL-2 and CASPASE-8 genes and their participation in the resistance/susceptibility mechanism of these tumor cell lines.METHODS:To determine the IC50 values associated with Cisplatin and rhTRAIL, inhibition of cell growth was observed using MTT assays in two human OC cell lines (SKOV-3 and TOV-21G). The analysis of gene expression was performed using quantitative real-time polymerase chain reaction (qRT-PCR).RESULTS:Both cell lines had different susceptibility profiles to the tested drugs. In the SKOV-3 cell line, the IC50 values for cisplatin and for rhTRAIL were 270.83 ug/mL and 196.5 ng/mL, respectively. The same concentrations were used for TOV-21G. Different gene expression profiles were observed in each tested cell line. CASPASE-8 and TNFRSF10B expression levels could predict the response of both the cell lines to rhTRAIL alone or the response to a combination of rhTRAIL and cisplatin. In addition, we observed a relationship between BCL-2 and BAX expression that may be helpful in estimating the proliferation rate of the OC cell lines.CONCLUSION:SKOV-3 and TOV-21G respond differently to cisplatin and rhTRAIL exposure, and expression of CASPASE-8 and TNFRSF10B are good predictors of responses to these treatments.
Highlights
Ovarian cancer (OC) is a highly fatal form of gynecological cancer characterized as the 7th most common cause of cancer in women worldwide [1,2]
The present study aims to determine the sensitivity of OC cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL, to evaluate the expression of TRAIL receptors (TNFRSF10B and TNFRSF10C), repair genes (TP53TG5 and MDM2), and apoptotic cascade genes (BAX, BCL-2, and CASPASE-8) in these cell lines, and to analyze their participation in drug resistance and drug susceptibility
We decided to use the IC50 values associated with cisplatin and recombinant human TRAIL (rhTRAIL) treatment of the SKOV-3 cells for experiments with TOV-21G cells in order to compare the effects of these drugs on each cell line
Summary
Ovarian cancer (OC) is a highly fatal form of gynecological cancer characterized as the 7th most common cause of cancer in women worldwide [1,2]. In 2018, OC was estimated to be responsible for 295,414 new cases of cancer and 184,799 deaths worldwide [3]. In Brazil, OC is 8th most common type of cancer in women. The estimated number of new OC cases in 2018-2019 was 6,150 [4] with an associated risk of 5.79 cases per 100,000 women.
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