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  • Molecular and histopathology study on the effects of Cisplatin and Naringenin in mice with induced breast cancer

  • Yaser Jafari-Khataylou,1 Bahareh Sadat Mirarabshahi,2 Masoumeh Firouzamandi,3,* Amir Ali Shahbazfar,4 Haniyeh Hosami Roudsari,5
    1. Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
    2. Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
    3. Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
    4. Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
    5. Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran


  • Introduction: Breast cancer remains one of the most common malignancies and a major cause of mortality in humans and animals. Despite the important role of surgery and chemotherapy in its management, treatment of advanced and metastatic disease is still challenging. Therefore, the present study aimed to investigate the therapeutic effects of Naringenin as a natural flavonoid compound with antioxidant and anticancer properties, alone and in combination with Cisplatin, on breast cancer in BALB/c mice.
  • Methods: In this experimental study,25 female BALB/c mice were inoculated with 4T1 breast cancer cells to establish a breast tumor model. The animals were divided into 5 groups, including: 1)non-cancer control, 2)cancer control, 3)Cisplatin-treated, 4)Naringenin-treated and 5)combined treatment group. Naringenin was administered orally at a dose of 50 mg/kg daily for 4 weeks, and Cisplatin was injected intraperitoneally at three dose (3 mg/kg) one day apart. At the end of the treatment period, tumor tissues were collected for RNA extraction, cDNA synthesis and quantitative real-time PCR analysis to evaluate the expression of breast cancer-related genes. Histopathological examinations were done on the collected samples in 10% formalin.
  • Results: Treatment with Naringenin influenced both tumor behavior and gene expression profiles, and these effects were more pronounced when Naringenin was applied with Cisplatin. A significant ( p<0.05) decrease in the expression of the anti-apoptotic gene Bcl-2 was observed in the combination treatment group. The expression level of the pro-apoptotic gene Bax was decreased in the combination treatment group and the Naringenin group compared to the control group ( p<0.05). The combined regimen showed a stronger antitumor effect than single agent, with greater inhibition of tumor progression and more favorable modulation of genes linked to apoptotic signaling and tumor proliferation.
  • Conclusion: These findings suggest that Naringenin may have potential as an effective natural anticancer agent and may enhance the therapeutic efficacy of Cisplatin in breast cancer treatment. Further studies are needed to clarify its mechanisms and evaluate its clinical applicability.
  • Keywords: Breast cancer, Cisplatin, combined treatment, Naringenin, Real-time RT-PCR

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