• Cytotoxic Effect of Simvastatin-loaded PCL-PEG nano-fiber scaffolds on 5-Fluorouracil-resistant MKN-45 Cell Lines of Gastric Cancer
  • Elham Norouz Dolatabadi,1 Vahid Asghariazar,2 Maryam Darvish,3 Kazem Nejati koshki,4,*
    1. Biotechnology department, Arak university of medical sciences, Arak, Iran
    2. Immunology research center, Ardabil university of medical sciences, Ardabil, Iran.
    3. Biotechnology department, Arak university of medical sciences, Arak, Iran
    4. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran


  • Introduction: Gastric cancer (GC) is one of the most common and invasive cancers in humans. According to GLOBOCAN 2018 data, Stomach cancer is the 5th most prevalent neoplasm and the 3rd most lethal malignancy. 5-Fluorouracil (5-FU) is extensively used in cancer treatment. However, drug resistance remains a major hurdle to 5-FU's therapeutic application. Therefore, new studies focus on the use of combination therapy as a new method of overcoming drug resistance. 3-Hydroxy-3-methyl glutaryl-CoA reductase inhibitors, known as statins, are commonly used to treat hypercholesterolemia, but their effects have also been proven to treat cancer. Simvastatin, a member of the statins family, has been shown to have anti-proliferative and apoptotic effects via upregulating and maintaining p53 phosphorylation. Simvastatin is very sensitive to hydrolytic conditions. Therefore, their physical encapsulation inside PCL-PEG (polycaprolactone-polyethylene glycol) as a hydrophilic biocompatible material can be a suitable method for the effective use of hydrophobic statins in the pharmaceutical industry. Our aim is to evaluate the cytotoxic effect of Simvastatin-loaded PCL-PEG scaffolds on 5-fluorouracil-resistant MKN-45 cells in Gastric cancer
  • Methods: The human GC MKN-45 cell line was supplied from the Pasteur Institute of Iran. RPMI-1640 culture medium containing 10% FBS complemented with 1% Penicillin Streptomycin solution was utilized to culture MKN-45 cells. The cells were maintained in T25 cell culture flasks in an incubator at 37°C with high humidity (95%) and 5% CO2. Simvastatin-loaded PCL-PEG nano-fiber scaffolds were designed by electrospinning and characterized by SEM and FTIR imaging. The scaffolds were cut to size and placed on the plate after sterilization. MKN-45-resistant 5-fluorouracil cells were then cultured on them. After 3 and 7 days, MTT assay and imaging of scaffolds were performed to determine the rate of cell proliferation on the scaffold.
  • Results: The MTT assay was performed to determine the effect of Simvastatin-loaded PCL-PEG scaffolds on cell viability. MTT test showed a significant increase in cell killing activity of Simvastatin released from PCL-PEG scaffold on MKN-45 cells (P <0.05). The results also show the time-dependent and dose-dependent effect of Simvastatin-loaded PCL-PEG scaffolds on 5-fluorouracil-resistant MKN-45 cells in Gastric cancer
  • Conclusion: The results of this study showed that Simvastatin loaded in PCL-PEG nano-fiber scaffold has the potential to inhibit proliferation and viability of 5-FU-resistant MKN-45 cell line. In addition, it can be concluded that Simvastatin loaded in PCL-PEG nano-fiber scaffold may be a suitable approach for combination therapy with drug 5-FU in Gastric cancer patients.
  • Keywords: Simvastatin, 5-Fluorouracil, PCL-PEG, Gastric cancer, Drug resistance