Increased sensitivity to cisplatin treatmentin mice with cervical cancer caused by TC-۱ cellline through the antitumor activity of oncolytic spores ofClostridium novyi-NT in hypoxic areas of the tumor.

Purpose: Despite the development of anti-HPV vaccines, cervicalCancer is still a common disease in women, especiallyin developing countries. The presence of a hypoxic microenvironmentcauses traditional treatments to fail. In this study, wepresented a combined treatment method based on the chemotherapeuticagent cisplatin and Clostridium novyi- NT spores totreat Normoxic and Hypoxic areas of the tumor.Materials and Methods: TC -۱ Cell line capable of expressingHPV-۱۶ E۶/۷ oncoproteins was subcutaneously transplantedinto female ۶-۸ week old C۵۷/BL۶ mice. The tumor-bearingmice were randomly divided into four groups and treated withdifferent methods after selecting a control group. Group ۱:Control without treatment (۰.۱ ml sterile PBS intratumorally),Group: C. novyi- NT (۱۰۷ C. novyi- NT).Group ۳: Receivescisplatin intraperitoneally (۱۰ mg/kg). fourth group: Intratumoraladministration of C. novyi- NT spores + intraperitonealcisplatin. Western blot analysis was used to examine the effectsof anti-hypoxia treatment and expression of HIF-۱ and VEGFproteins.Results: The results clearly showed that combined treatmentbased on C. novyi-NT and cisplatin significantly reduced theexpression of HIF-۱ alpha and VEGF proteins compared to cisplatinalone. At the same time, the amount of necrosis of tumorcells in the combined treatment increased significantly comparedto the single treatment and the control. At the same time,the mitonic count decreased significantly.Conclusion: Our research showed that developing a combinedtreatment method based on C. novyi-NT and cisplatin againstHPV-positive cervical Cancer could overcome the treatmentlimitations caused by the existence of hypoxic areas of the tumor.

کلیدواژه ها:

Clostridium novyi-NT ، Cisplatin ، TC-۱ Cell line ، cervicalcancer ، Tumor Hypoxia