Objective: Ovarian cancer is one of the most common gynaecological malignancies among females worldwide. Early diagnostic of ovarian cancer is challenging, and miRNAs could serve as a potential biomarker for early detection of ovarian cancer regarding easy to detect. The present study investigated the expression profile of miRNA-34a, miRNA-143, miRNA-212, Sox4, BCL-2, and E2f5 in the serum of participants to find new biomarkers for early diagnosis of ovarian cancer. Materials and Methods: Five milliliters of whole blood were collected from each patient (n=30) and control (n=30), and total RNA was extracted using Ambion™ TRIzol™ Reagent. Real-time PCR methods evaluated the expression of targeted miRNAs and their targeted genes. Result: The Disease status of all ovarian cancer patients were classified as FIGO stage III (21) and (IV 9) according to imaging studies and surgical pathological findings. Our results showed that expression levels of miRNA-34a (p<0.0001), miRNA-143 (p=0.028), and miRNA-212 (p<0.0001) were significantly decreased in patients with ovarian cancer compared to controls and expression levels of Sox4(p<0.0001), BCL-2(p<0.0001) and E2f5(p<0.0001) were significantly increased in patients with ovarian cancer compared to controls. In addition, Receiver Operating Characteristic (ROC) curve revealed that the expression profile of miRNA-34a (AUC= 0.82; P <0.0001), miRNA-143 (AUC= 0.66; P = 0.026) and miRNA-212 (AUC= 0.78; P = 0.0001) could be used as potential biomarker for discriminating patients with ovarian cancer. Conclusion: In conclusion, our data showed that the expression profile of miRNA-34a, miRNA-143, and miRNA-212 could act as a potential biomarker for diagnosing ovarian cancer patients.
Objective Ovarian cancer is one of the most common gynaecological malignancies among females worldwide. Early diagnostic of ovarian cancer is challenging, and miRNAs could serve as a potential biomarker for early detection of ovarian cancer regarding easy to detect. The present study investigated the expression profile of miRNA-34a, miRNA-143, miRNA-212, Sox4, BCL-2, and E2f5 in the serum of participants to find new biomarkers for early diagnosis of ovarian cancer. Materials and Methods Five milliliters of whole blood were collected from each patient (n = 30) and control (n = 30), and total RNA was extracted using Ambion™ TRIzol™ Reagent. Real-time PCR methods evaluated the expression of targeted miRNAs and their targeted genes. Result The Disease status of all ovarian cancer patients were classified as FIGO stage III (21) and (IV 9) according to imaging studies and surgical pathological findings. Our results showed that expression levels of miRNA-34a (p < 0.0001), miRNA-143 (p = 0.028), and miRNA-212 (p < 0.0001) were significantly decreased in patients with ovarian cancer compared to controls and expression levels of Sox4(p < 0.0001), BCL-2(p < 0.0001) and E2f5(p < 0.0001) were significantly increased in patients with ovarian cancer compared to controls. In addition, Receiver Operating Characteristic (ROC) curve revealed that the expression profile of miRNA-34a (AUC = 0.82; P < 0.0001), miRNA-143 (AUC = 0.66; P = 0.026) and miRNA-212 (AUC = 0.78; P = 0.0001) could be used as potential biomarker for discriminating patients with ovarian cancer. Conclusion In conclusion, our data showed that the expression profile of miRNA-34a, miRNA-143, and miRNA-212 could act as a potential biomarker for diagnosing ovarian cancer patients.
Background: Multidrug resistance (MDR) is a major cause of unsuccessful cancer treatment in which drugs are not effective. Therefore, it is necessary to identify the critical mechanisms of the development of MDR and target those with novel compounds. Accordingly, the current study is the first to investigate the combination effect and molecular mechanism of nitazoxanide (NTZ) and oxaliplatin (OXP) on LS174T/OXP-resistant cells. Methods: The effect of NTZ on OXP cytotoxicity in LS174T and LS174T/OXP cell lines was evaluated by MTT assay. Changes in expression levels of MDR1, MRP1, CTNNB1, peptidylarginine deiminase (PAD)2, and PAD4 genes and proteins were evaluated by RT-qPCR and western blotting methods, respectively. Lastly, the apoptosis assay was performed by flow cytometer. Results: OXP resistant and sensitive cells were identified based on the IC 50 values (11567 nM vs. 1745 nM, p<0.05 for 24 h treatment; and 5161 nM vs. 882 nM, p<0.05 for 48 h incubation). The combination of NTZ and OXP for 48 h led to a reduction in IC 50 values in resistant cells (2154 nM, p<0.05). The effect of NTZ plus OXP significantly decreased the expression of MDR1 (p<0.001), MRP1 (p<0.05), and CTNNB1 (p<0.001), while PAD2 and PAD4 expression was significantly increased (p<0.001). This combination therapy enhanced the percentage of the sub-G1 population (apoptosed) compared to other groups. Conclusion: The results showed that NTZ leads to notable upregulation of PAD2 and PAD4, which can disrupt the Wnt/β-catenin signaling pathway and reverse the MDR by reducing MDR1 and MRP1 expression.
Object(s): Shortly after cancer is diagnosed, a phenomenon develops in cancer cells called multidrug resistance (MDR) in which cell sensitivity against anti-cancer drugs is significantly reduced. The present investigation aimed to assess the effects of nitazoxanide (NTZ), a safe drug, on LS174T/OXP-resistant cells. Method(s) and strategy: In the current in vitro research, the effects of NTZ and oxaliplatin (OXP) on the viability of LS174T and LS174T/OXP cell lines were evaluated through MTT assay. Then, the changes in expression levels of MDR1, MRP1, BCRP, and LRP genes and proteins were measured by RT-qPCR and western blotting methods, respectively. Lastly, the apoptosis status was assessed by annexin V–FITC/PI staining flow cytometry assay. Results: The IC50 values for cells resistant or sensitive to OXP were revealed (11567 nM vs. 1745 nM; p <0.05 for 24 h incubation, and 5161 nM vs. 882.2 nM; p <0.05 for 48 h incubation). Moreover, NTZ plus OXP led to a leftward shift in the cytotoxicity curve (2004 nM; p = 0.007). This co-treatment significantly decreased the expression of all genes and proteins (p <0.05). Finally, the combination of NTZ and OXP induced a significant increase in apoptosis (p <0.001). Conclusion: The data showed that NTZ treatment could increase the sensitivity of LS174T/OXP cell line to the OXP cytotoxic effects. Thus, NTZ may be efficient in reducing drug resistance in clinics by means of the negative regulation of ATP-binding cassette (ABC) transporters. However, further studies are necessary to explain the exact mechanisms of NTZ.
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