Abstract
Objective:The purpose of the current study was to investigate the possible anti-tumor effect of miR-27a inhibitor in combination with Sorafenib (SOR) on cell proliferation and apoptosis of hepatocellular carcinoma cell lines. Methods:Transient transfection by oligo-miR27a inhibitor (miR-27ai) was used in this study for targeting the oncogenic miR-27a in HepG2 and Huh7 cells followed by SOR treatment. Cell viability was measured using SRB assay. The cell cycle and apoptosis were assessed by flow cytometry assay. Moreover, the level of oncogenic miR-27a was evaluated in 19 tissues of primary HCC patients as well as cell lines using qRT-PCR assay. Finally, caspase-3 activity was determined using ELISA assay. Results:Significant up-regulation of miR-27a expression was reported in HCC patients confirming its oncogenic role. Treatment of cells with SOR following transfection with miR-27ai declined cell viability significantly compared with either control or single agent treatment (p≤0.05). Highly significant decreasing in the number of cell in S-phase associated with increasing in G0-phase was also observed. Furthermore, apoptotic rate was highly significantly increased for transfected/SOR treated cells (p≤0.01). Finally, combination treatment demonstrated a significant elevation of caspase-3 activity level in both cell lines examined. Conclusion:The present data demonstrated targeting miR-27a enhances the anti-tumor effect of SOR in HCC cell lines considering as one of the promising therapeutic targets for advanced HCC management.
Highlights
Hepatocellular carcinoma (HCC) is considered as one of the most commonly diagnosed malignancies and the third-leading cause of cancer-related death in the world after lung and stomach
Effect of sorafenib on cell proliferation Both cell lines used in the present study (HepG2/Huh7)
While, combined treatment of miR-27a inhibitor with sorafenib (IC20) resulted in a significant inhibition in cell viability by 40% and 71% in HepG2 cells and Huh7 respectively compared to NTC (p < 0.05)
Summary
Hepatocellular carcinoma (HCC) is considered as one of the most commonly diagnosed malignancies and the third-leading cause of cancer-related death in the world after lung and stomach. HCC incidence mainly associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections (Ghouri et al, 2017). HCC has a very low overall 5-year survival rate due to lake of definite and accurate diagnostic tools in its early stages (Golabi et al, 2017). Low survival benefits were recorded for late-stage HCC patients received systemic chemotherapeutic agents (Liu et al, 2015). Despite the fact that sorafenib has been approved in several countries worldwide for advanced HCC patients still yet the drug show unsatisfied clinical outcomes due to its severe side effects as well as drugresistanceleadingto tumor progression and recurrence (van Malenstein et al, 2013). Resistance to treatment, tumor recurrence and metastasis shed the light of the importance of providing novel effective therapeutic tactics able to enhance the clinical outcome for HCC patients
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