• Comparison of the effect of exosomes secreted from stem cells derived from menstrual blood And ginger plant exosomes on apoptosis and migration of ovarian cancer cell line SKOV-3
  • afsaneh razaghi,1 Azar Sheikholeslami,2,* Zahra Zamanzadeh,3 Hoda Fazaeli,4
    1. Department of Genetics, Faculty of Biological Sciences and Technology, Shahid Ashrafi Esfahani University, Isfahan, Iran
    2. Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
    3. Department of Genetics, Faculty of Biological Sciences and Technology, Shahid Ashrafi Esfahani University, Isfahan, Iran
    4. Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran


  • Introduction: Ovarian cancer is the most common fatal malignancy of the female genital tract, which is often diagnosed in advanced stages. Many different approaches are utilized to treat ovarian cancer, including surgery, radiotherapy, and chemotherapy. Still, due to their unsatisfactory effectiveness, researchers are searching for new strategies to lengthen patients' lives and prevent the adverse effects of earlier therapies. Recently, the utilization of cell therapies has increased for a variety of diseases, including cancers, due to the nature of stem cells. These cells exert their therapeutic effects in a paracrine manner. Exosomes with a diameter of 30 to 100 nanometers and a bilayer lipid membrane as a kind of extracellular vesicles (EVs) are thought to be a new treatment option due to their small size, ability to pass through membranes while protecting the proteins and RNAs inside from degradation, and capacity to transport a variety of substances (1). So they occasionally have lower prices, a higher rate of therapy success, and fewer negative side effects than cell therapy for the patient. On the other hand, ginger is known by its inhibitory effects on cancer through reducing oxidative stress and inducing natural cell death. The active compounds of this plant such as gingerol and shogaol are well able to inhibit the production of inflammatory prostaglandins, nitric oxide inhibitors and even interleukins involved in inflammation and in all stages of tumorogenesis, while it has been documented that ginger extract has anti-cancer properties against malignancies of the colon (2), skin (3), liver, breast (2), prostate (4), endometrium (5) and ovary (6). Fresh fruits, vegetables, and plant seeds can all be used to obtain plant exosomes, one of the extracellular nanovesicles of plants. The aim of this study is to compare the effects of exosomes derived from menstrual blood-derived mesenchymal stem cells (C-Exo) and ginger plant-derived exosomes (P-Exo) on the migration and apoptosis pathway in ovarian cancer Skov3 cells.
  • Methods: Ovarian cancer cells of SKOV-3 type were purchased from Enyisto-Pasteur Center of Iran. It was cultured In RPMI1640 medium containing 10% bovine serum (FBS) and 1% biotic ratio. The isolation of C- and P-exosomes from NE-MenSCs conditioned medium and ginger extract, respectively, was. Using the Bradford test, cell growth was made. In order to determine the effective dosage of exosomes for treatment, cell viability was evaluated by methyl thiazole tetrazolium (MTT) assay in 0, 50, 100, 200 and 300 μg/ml concentrations. Skov3 cells were used in the 3rd passage. Following 70% confluence, the C- and P-Exo (50 and 100 μg/ml) was added to DMEM containing 10% FBS and 1% penicillin-streptomycin per well. The cells were incubated for 48 h in standard condition, and then the level of apoptosis and expression level of Bax, Bcl2, MMP2, and MMP9 using Annexin V/PI and real time PCR, respectively.
  • Results: Exosomes obtained from ginger and MenSCs Increase the survival of skov3 cells in a dose- and time-dependent manner, but the effect of C-Exos has a significant effect on the survival of ovarian cells and increases Bax and Bcl2 gene expression, while decrease the expression of MMP2 and MMP9 genes. As a result, according to the Annexin V/PI assay, C-Exo has a significant effect on the apoptosis of cancer cells.
  • Conclusion: The results of this study show that C-EXO has time- and dose-dependent inhibitory effect on Skov3 cells, so with further research in the future, this compound can be used to develop anti-ovarian cancer drugs.
  • Keywords: ovarian cancer cells - SKOV-3 cell line - exosome - mesenchymal stem cells - ginger - apoptosis