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.
ABSTRACT
Resistance to conventional antitumour therapies and Hypoxia in patients with advanced solid tumours are two major reasons for the failure of conventional anti-tumour therapies. Therefore, it is important to find a new therapeutic method that can overcome these problems. An attenuated anaerobic bacterium, Clostridium novyi-NT, could target Hypoxic and Necrotic areas of tumours causing tumour lysis and stimulating a host anti-tumour immune response. To the best of our knowledge, the combination of bacterial anti-tumour therapy, chemotherapy, radiotherapy and immunotherapy may promote tumour regression, inhibit metastasis and develop a new strategy for the treatment of solid tumours. However, the possible molecular mechanisms of the combined therapies are still the biggest challenge. This review provides an overview of the history of bacterial cancer therapy and the development of a non-lethal strain of Clostridium novyi. Below is a precise definition of Hypoxic conditions in solid tumour tissue. To understand the anticancer effect of Clostridium novyi-NT spores, possible cell death mechanisms were summarised by the enzyme phospholipase C (nt01cx0979), which is secreted by Clostridium novyi-NT spores after germination in tumour tissue. The function of Clostridium novyi-NT spores in stimulating the host immune system to elicit anti-tumour responses was reviewed. Then, the results of anti-tumour combination therapies based on Clostridium novyi-NT spores were compiled. Identifying the molecular mechanisms of Clostridium novyi-NT in treating tumours and inducing cell death in invasive cancer cells, ultimately leading to tumour regression, may develop promising clinical strategies in the combined treatment of solid tumours.
