In:
Advanced Pharmaceutical Bulletin, Maad Rayan Publishing Company, ( 2023-05-20)
Abstract:
Purpose: Despite developing anti-HPV vaccines, cervical cancer is still a common disease among women, especially in developing countries. The presence of hypoxic microenvironments causes the failure of traditional treatment methods. In this research, we presented a combined treatment method based on the chemotherapy agent cisplatin and Clostridium novyi-NT spores to treat normoxia and hypoxic areas of the tumor. Methods: TC-1 cell line with the ability to express HPV-16 E6/7 oncoproteins was transplanted subcutaneously to female 6-8 weeks old C57/BL6 mice. The tumor-bearing mice were randomly divided into 4 groups and after choosing a control group, they were treated with different methods. The first group: control without treatment (0.1 ml of sterile PBS intratumoral), the second group: C. novyi-NT (107 C. novyi-NT). The third group: receiving cisplatin intraperitoneally (10 mg/kg). Fourth group:receiving C. novyi-NT spores intratumorally + intraperitoneal cisplatin. Giemsa staining and Real-time PCR were used to identify spore germination in mice receiving spores. Western blot analysis was used to investigate the effects of anti-hypoxia treatment, the expression of HIF-1 and VEGF proteins. ELISA method was used to measure the amount of Western blot analysis. Results: The results clearly showed that combined treatment based on C. novyi-NT and cisplatin significantly reduced the expression of HIF-1 alpha and VEGF proteins compared to cisplatin alone. Also, the amount of ROS was significantly reduced in the combined treatment compared to the control group and cisplatin-only therapy. The amount of necrosis of tumor cells in the combined treatment increased significantly compared to the single treatment and the control, and at the same time, the mitonic count decreased significantly. Conclusion: Our research showed that the development of a combined treatment method based on C. novyi-NT and cisplatin against HPV-positive cervical cancer could overcome the treatment limitations caused by the existence of hypoxic areas of the tumor.
Type of Medium:
Online Resource
ISSN:
2228-5881
,
2251-7308
DOI:
10.34172/apb.2023.084
Language:
English
Publisher:
Maad Rayan Publishing Company
Publication Date:
2023
detail.hit.zdb_id:
3018440-X
