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CancerGenetics

• Studying the effects of Cisplatin and Artemisinin on the expression of apoptosis-related genes in mice

• Haniyeh Hosami Roudsari,¹ Masoumeh Firouzamandi,^2,* Yaser jafari-khataylou,³ Amir Ali Shahbazfar,⁴ Bahareh Sadat Mirarabshahi,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: Cisplatin is a chemotherapeutic drug widely used in the treatment of various types of cancer; however, its use is often limited due to side effects and the developement of drug resistance. Artemisinin is a plant-drived compound found in plants of the Artemisia genus and shown a wide range of therapeutic effects including antiviral, antiparasitic and anticancer properties. The present study aimed to investigate the therapeutic effects of Artemisinin as a compound with anticancer properties, alone and in combination with Cisplatin, on on breast cancer in BALB/c mice.
• Methods: A total of 25 female BALB/c mice aged 5-6 weeks were divided into five groups: (1) cancer control group (infected group without treatment), (2) non-cancer control group, (3) Cisplatin-treated group, (4) Artemisinin-treated group and (5) combination treatment group. Each mouse in all groups except the non-cancer control group was injected with one million 4T1 cells. Artemisinin (150mg/kg) for 4 weeks orally and Cisplatin (3mg/kg) in three doses intraperitoneally and one day apart, were administered to the respective groups. The expression levels of breast cancer-related genes in tissue samples were evaluated using Real-time RT-PCR. Histopathological examinations were done on the collected samples in 10% formalin.
• Results: The morphology results showed that the tumor size was reduced in the combination treatment group. A significant (p<0.001) increase in the expression of the pro-apoptotic gene Bax was observed in the combination tratment group. The expression level of the anti-apoptotic gene Bcl-2 was slightely increased in the combination treatment group and the Artemisinin group compared to the control group, while it was decreased in the Cisplatin group (p<0.05). Among all the experimental groups, the most effective treatment response was observed in the combination treatment group. Histopathological examinations showed that although there was a relative decrease in cell density and more uniform nuclear shape in company with some degree of necrosis and hemorrhage in the single-drug treatment (in both Cisplatin or Artemisinin) groups compared to the cancer control group. Whereas, in the combination treatment group, in addition to a significant (p<0.05) decrease in cell density and more uniform nuclear shape, no hemorrhage or necrosis was observed.
• Conclusion: These findings suggest a complementary interaction between Artemisinin and Cisplatin that enhances tumor supression. On the other word, results of the present study suggest that combination therapy produced the strongest antitumor response and showed better histopathological characteristics than single agent therapy. It seems that combination treatment with Artemisinin and Cisplatin may be a promising approach for future cancer treatment.
• Keywords: Artemisinin, Breast cancer, Cisplatin, Combination treatment, Real-time RT-PCR