مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Exosomes derived from Stem Cells enhance Etoposide-induced apoptosis in HepG2 Cells
Exosomes derived from Stem Cells enhance Etoposide-induced apoptosis in HepG2 Cells
Elham Shakerian,1,*samane salehipoor,2Mahdi Hatami,3
1. 1-Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2-Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 3. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Introduction: Hepatocellular carcinoma (HCC) represents the most common type of liver malignancy in the world. Traditional cancer treatment approaches, like chemotherapy and radiotherapy, often pose significant risks to patients, including potential organ damage and inflammation, even in severe cases, death. Etoposide (ETO), a widely used chemotherapeutic agent, is not exempt from these complications. For years, combinational therapies have been explored as promising strategies to enhance treatment efficacy while mitigating adverse side effects. Stem cell-derived exosomes, recognized for their therapeutic potential, have emerged as valuable tools in cancer treatment due to their anti-cancer properties.
In this study, we investigate the potential synergistic effects between stem cell-derived exosomes and etoposide (ETO) in inducing apoptosis in HepG2 hepatocellular carcinoma cells.
Methods: Cell apoptosis was evaluated using Annexin V/PI staining along with caspase-3 and -9 activity assays. Gene expression of Bax and Bcl-2 was measured by qRT-PCR. p53 protein levels were assessed using western blotting.
Results: Treatment with both stem cell-derived exosomes (100 µg/mL) and etoposide (10 µM) significantly reduced HepG2 cell viability and induced apoptosis (16.2%), compared to either treatment alone. Caspase-9 and -3 activities increased to 69% and 64% respectively, under combined treatment, versus 33% and 31% with exosomes and 51% and 39% with ETO alone. Bax expression rose by 3.6-fold and Bcl-2 decreased to 0.44-fold upon co-treatment, leading to a markedly elevated Bax/Bcl-2 ratio. Moreover, p53 protein levels increased 3.24-fold, highlighting the enhanced apoptotic signaling. These results confirm a synergistic effect between exosomes and ETO
Conclusion: Our findings revealed that stem cell-derived exosomes exhibit synergistic effects when co-treated with etoposide (ETO) in HepG2 cells. Building on these results, we conclude that further investigation of this combination could lead to the development of a promising anti-cancer therapy for hepatocellular carcinoma (HCC) and a Novel strategy for enhanced chemotherapy in HCC.