Sildenafil enhances cisplatin-induced apoptosis in human breast adenocarcinoma cells.

INTRODUCTION: Cyclic nucleotide phosphodiesterase (PDE) enzymes are a large superfamily of enzymes that catalyze the conversion reaction of cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) to AMP and GMP, respectively. In some cancer cells, PDE-5 has been shown to be overexpressed in multiple human carcinomas. It seems that the inhibition of PDE-5 may has anticancer effects. Cisplatin is one of the prevalent chemo-agents to treat solid tumors. However, its clinical usefulness is hindered by dose-limiting toxicities, especially on the kidneys (nephrotoxicity) and ears (ototoxicity). In this study, the antitumor activity of the sildenafil as a PDE-5 inhibitor alone and in combination with cisplatin on human mammary adenocarcinomas and MCF-7 and MDA-MB-468 was assessed. MATERIALS AND METHODS: Sildenafil as PDE type 5 (PDE5) inhibitor is the drugs that we combined with the cisplatin (chemotherapeutic agent), in vitro. Human mammary adenocarcinomas and MCF-7 and MDA-MB-468 cell lines were cultured in standard conditions. At time point, following 24 h and 48 h incubation, the cell lines were treated by cisplatin in the presence/absence of sildenafil. Cell viability, apoptosis, and reactive oxygen species (ROS) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, real-time polymerase chain reaction, and Western blot; and fluorimetric methods, respectively. Statistical analysis was performed using SPSS software SPSS (SPSS Inc., Chicago, IL, USA). RESULTS: In MCF-7 cell line, following 24 h incubation, combinations of sildenafil with cisplatin (P < 0.001) showed decreased cell viability when compared to sildenafil and cisplatin alone. Moreover in MDA-MB-468 cell line, following 24 h incubation, data did not show any significant changes on cell viability when treated with cisplatin, in the presence or absence of sildenafil. However, following 48 h incubation, combinations of cisplatin with sildenafil (P < 0.001) were showed decreased cell viability when compared to cisplatin and sildenafil alone in both MCF-7 and MDA-MB-468 cell lines. Concerning the ROS production and apoptosis, data showed that both processes increase significantly in the presence of the sildenafil in comparison absent it. CONCLUSION: Our data showed that the combination of sildenafil with cisplatin can improve cell toxicity and anticancer effect of cisplatin. And also sildenafil as a PDE-5 inhibitor could be used as additive treatment in combination with cisplatin to make a reduction in cisplatin dosage and its side effects.

Correlations between Overexpression of SOX2OT Long Non-coding RNA and Susceptibility to Breast Cancer.

BACKGROUND AND OBJECTIVE: The SOX2OT lcnRNA has been recognized as a positive regulator in the transcription regulation of the SOX2 gene. Recent studies have approved the dysregulation of SOX2OT lncRNA expression patterns in some common cancer types, including esophageal, lung, and breast cancer. The objective of the present study was to investigate the correlation between overexpression of SOX2OT lcnRNA and susceptibility to breast cancer. METHODS: SOX2OT lncRNA expression profiling in 15 breast cancer and normal tumour-adjacent breast tissue samples was performed by using qRT-PCR. To evaluate the diagnostic potential of the SOX2OT lncRNA, we performed ROC curve analyses. RESULTS: The expression of SOX2OT lncRNA in patients suffering from breast cancer revealed a significant overexpression in comparison with the healthy group (P<0.001). Significantly, the elevated circulating SOX2OT lncRNA was found specific to breast cancer and could differentiate breast cancer from controls with 100% of both sensitivity and specificity. Based on the Kaplan- Meier analysis, there was no significant correlation between SOX2OT lcnRNA expression and overall survival. CONCLUSION: The results confirmed the association between breast cancer and higher SOX2OT lncRNA expression. According to the ROC curve results, SOX2OT lcnRNA could be a new measurable indicator of the breast cancer and a potential therapeutic target for breast cancer patients.