Anti-tumor Effects of Cisplatin Synergist in Combined Treatment with Clostridium novyi-NT Spores Against Hypoxic Microenvironments in a Mouse Model of Cervical Cancer Caused by TC-1 Cell Line

Author:

Ebadi Sharafabad Behrouz1ORCID,Abdoli Asghar2,Panahi Mohammad2,Abdolmohammadi Khiav Lida3,Jamur Parisa2,Abedi Jafari Fatemeh4,Dilmaghani Azita15ORCID

Affiliation:

1. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

2. Department of Hepatitis and HIV, Pasteur Institute of Iran (IPI), Tehran, Iran.

3. Department of Anaerobic Vaccine Research and Production, Specialized Clostridia Research Laboratory, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran.

4. Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

5. Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

Purpose: Despite the development of anti-human papillomavirus (HPV) vaccines, cervical cancer is still a common disease in women, especially in developing countries. The presence of a hypoxic microenvironment causes traditional treatments to fail. In this study, we presented a combined treatment method based on the chemotherapeutic agent cisplatin and Clostridium novyi-NT spores to treat normoxic and hypoxic areas of the tumor. Methods: TC-1 Cell line capable of expressing HPV-16 E6/7 oncoproteins was subcutaneously transplanted into female 6-8 week old C57/BL6 mice. The tumor-bearing mice were randomly divided into four groups and treated with different methods after selecting a control group. Group 1: Control without treatment (0.1 mL sterile PBS intratumorally), Group: C. novyi-NT (107 C. novyi- NT). Group 3: Receives cisplatin intraperitoneally (10 mg/kg). Fourth group: Intratumoral administration of C. novyi-NT spores+intraperitoneal cisplatin. Western blot analysis was used to examine the effects of anti-hypoxia treatment and expression of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins. 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. At the same time, the amount of necrosis of tumor cells in the combined treatment increased significantly compared to the single treatment and the control. At the same time, the mitotic count decreased significantly. Conclusion: Our research showed that developing 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.

Publisher

Maad Rayan Publishing Company

Subject

General Pharmacology, Toxicology and Pharmaceutics,Pharmaceutical Science

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