Background:: Salinomycin is part of a group of ionophore antibiotics characterized by an activity towards tumor cells. To this day, the mechanism through which salinomycin induces their apoptosis is not fully known yet. The goal of this study was to assess the expression pattern of genes and the proteins coded by them connected with the process of programmed cell death in an endometrial cancer cell Ishikawa culture exposed to salinomycin and compared to the control. Material and methods: Analysis of the effect of salinomycin on Ishikawa endometrial cancer cells (ECACC 99040201) included a cytotoxicity MTT test (with a concentration range of 0.1-100 µM), assessment of the induction of apoptosis and necrosis by salinomycin at a concentration of 1 µM as well the assessment of the expression of the genes chosen in the microarray experiment (microarray HG-U 133A_2) and the proteins coded by them connected with apoptosis (RTqPCR, ELISA assay). The statistical significance level for all analyses carried out as part of this study was p<0.05. Results: It was observed that salinomycin causes the death of about 50% of cells treated by it(50.74±0.80 % of all cells) at a concentration of 1µM. The decrease in the number of living cells was determined directly after treatment of the cells with the drug (time 0). The average percent of late apoptotic cells was 1.65±0.24% and 0.57±0.01% for necrotic cells throughout the entire observation period. Microarray analysis indicated the following number of mRNA differentiating the culture depending on the time of incubation with the drug: H_12 vs C = 114 mRNA, H_8 vs C = 84 mRNA, H_48 vs C = 27 mRNA, whereas 5 mRNA were expressed differently at all times. During the whole incubation period of the cells with the drug, the following dependence of the expression profile of the analyzed transcripts was observed: Bax>p53>FASL>BIRC5>BCL2L. Conclusions: The analysis that was carried out indicated that salinomycin, at a concentration of 1 µM, stops the proliferation of 50% of endometrial cancer cells, mainly by inducing the apoptosis process of the cells. The molecular exponent of the induction of programmed cell death was an observed increase in the transcriptional activity of pro-apoptotic genes: Bax;p53;FASL and a decrease in the expression of anti-apoptotic genes: BCL2L2; BIRC5.

Background: Salinomycin, an ionophore antibiotic, has a strong anti-cancer effect, inducing the apoptosis of cancer cells and cancer stem cells. Objective: The aim of the study was to assess the influence of salinomycin on the expression profile of genes related to stemness and miRNA regulating their expression in endometrial cancer cells. Methods: Endometrial cancer cells of cell line Ishikawa were exposed to salinomycin at concentrations in the range of 0.1- 100 µM, with the aim of determining its pro-apoptotic potential and the concentration which would cause the death of 50% of the cells (Sulforhodamine B test). In the following stages, the cells were incubated with the drug at a concentration of 1µM for 12,24 and 48 hour periods and compared to the control. Determining the changes in the expression of the genes related to stemness and regulating their miRNA was done using the microarray technique and RTqPCR. ELISA assay was performed in order to determining the level of TGFβ2, COL14A1, CDH2, WNT5A in cell culture under salinomycin treatment in comparison to the control. Results: Salinomycin caused the apoptosis of cells. For the concentration of 0.1 µM, a decrease in the population of living cells by 11.9% was determined. For 1 µM, it was 49.8%, for 10 µM -69.4%, and for a concentration of 100 µM - 87.9%. The most noticeable changes in the expression caused by the addition of salinomycin into the culture were noted for mRNA: TGFβ2; WNT5A (up-regulated); COL14A1; CDH2 (down-regulated), as well as miRNA: hsa-miR-411 (up-regulated); hsamiR-200a; hsa-miR-33a; hsa-miR-199a; hsa-miR-371-5p; hsa-miR-374; hsa-miR-374b (down-regulated). Conclusion: It was confirmed that salinomycin has the influence for the stemness process. The most noticeable changes in the expression were noted for mRNA: TGFβ2; COL14A1; CDH2; WNT5A, as well as for miRNA: hsa-miR-200a; hsa-miR33a; hsa-miR-199a; hsa-miR-371-5p; hsa-miR-411; hsa-miR-374a; hsa-miR-374b.

Background: Semaphorin 3B (SEMA3B) is characterized as a strong suppressing factor of the proliferation of cancerous cells and also by its anti-angiogenic effect. However, the knowledge on the changes in the expression profile of SEMA3B under the influence of cisplatin in endometrial cancer remains fragmented. The aim of this work was to note the changes in expression of SEMA3B when under the influence of cisplatin in the endometrial cancer cell line. Methods: Ishikawa cell line cells were exposed to three different concentrations of cisplatin: 2.5µM; 5µM; 10µM for 12,24 and 48 hour periods and were compared to cells untreated by the drug. Changes in the expression profile of SEMA3B were determined based upon RtqPCR (mRNA) alongside the ELISA assay (protein). The Statistica 13.0 PL program was used for statistical analysis (p<0.05). Results: Changes on the transcriptome level seem to be more dynamic than on the proteome level. Regardless of the concentration given or the exposition period, the expression of semaphorin 3B was, in fact, higher in cells exposed to cisplatin. Statistically substantial differences (p<0.05) in the expression of SEMA3B mRNA and protein were seen for all incubation periods at the given cisplatin level when compared to the control. Conclusions: Cisplatin causes a growth in the expression of SEMA3B in a endometrial cancer cell culture, this results in the restoration in the state of cell homeostasis and shows the effectiveness of pharmacotherapy, including a low risk of drug resistance.

The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein–Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages.