Volume 35, Issue 2 (May 2024)                   Studies in Medical Sciences 2024, 35(2): 93-106 | Back to browse issues page

Research code: 64371
Ethics code: IR.TBZMED.VCR.REC.1398.434)


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Ebadi Sharafabad B, Dilmaghani A. INDUCTION OF REGRESSION OF CERVICAL CANCER CAUSED BY HPV INFECTION IN A MOUSE MODEL USING COMBINATION THERAPY BASED ON CLOSTRIDIUM NOVYI-NT SPORES AND CISPLATIN THROUGH REDUCTION OF E6. Studies in Medical Sciences 2024; 35 (2) :93-106
URL: http://umj.umsu.ac.ir/article-1-6204-en.html
Associate Professor of Pharmaceutical Biotechnology, Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran (Corresponding Author) , dilmaghani.a@gmail.com
Abstract:   (876 Views)
Background & Aims: Despite the development of anti-human papillomavirus (HPV) vaccines, cervical cancer is still a common disease in women, especially in developing countries. The existence of a hypoxic microenvironment causes the failure of traditional treatments. In this study, a combined treatment method based on cisplatin and Clostridium novyi-NT is proposed for the treatment of cervical cancer.
Materials & Methods: The TC-1 cell line, which is capable of expressing HPV-16 E6/7 oncoproteins, was transplanted subcutaneously into the right flank of 6–8-week-old female C57/BL6 mice. Tumor-bearing mice were randomly divided into four groups, and after selecting the control group, they were treated with different methods, including combined treatment based on cisplatin and bacterial spores. Western blot analysis was used to investigate the effects of antihypoxia treatment and the expression of P53 tumor suppressor proteins, and RT-PCR was used to measure changes in the expression of E6, Bax, and Bcl-2 genes.
Results:  This study clearly showed that a combined treatment with C. novyi-NT and cisplatin significantly increased the expression of the p53 tumor suppressor protein compared with cisplatin alone. Simultaneously, this combined treatment causes regression of tumor size and decreased expression of the E6 carcinogenic gene related to human papilloma virus.
Conclusion: This study showed that the development of a combined treatment method based on C. novyi-NT and cisplatin against cervical cancer can overcome the treatment limitations caused by the hypoxic areas of the tumor.
 
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Type of Study: Research | Subject: میکروبیولوژی

References
1. Wardak S. Human Papillomavirus (HPV) and cervical cancer. Med Dosw Mikrobiol 2016;68(1):73-84. [PMID]
2. Mittal S, Banks L. Molecular mechanisms underlying human papillomavirus E6 and E7 oncoprotein-induced cell transformation. Mutat Res - Rev Mutat Res 2017;772:23-35. [DOI:10.1016/j.mrrev.2016.08.001] [PMID]
3. Spayne J, Hesketh T. Estimate of global human papillomavirus vaccination coverage: analysis of country-level indicators. BMJ Open 2021;11(9):e052016. [DOI:10.1136/bmjopen-2021-052016] [PMID] []
4. Davies-Oliveira J, Smith M, Grover S, Canfell K, Crosbie E. Eliminating cervical cancer: progress and challenges for high-income countries. Clin Oncol 2021;33(9):550-9. [DOI:10.1016/j.clon.2021.06.013] [PMID]
5. Vaupel P. Pathophysiology of solid tumors. The impact of tumor biology on cancer treatment and multidisciplinary strategies: Springer; 2009. p. 51-92. [DOI:10.1007/978-3-540-74386-6_4]
6. Bossler F, Kuhn BJ, Günther T, Kraemer SJ, Khalkar P, Adrian S, et al. Repression of human papillomavirus oncogene expression under hypoxia is mediated by PI3K/mTORC2/AKT signaling. MBio 2019;10(1):10.1128/mbio. 02323-18. [DOI:10.1128/mBio.02323-18] [PMID] []
7. Hoppe-Seyler K, Bossler F, Lohrey C, Bulkescher J, Rösl F, Jansen L, et al. Induction of dormancy in hypoxic human papillomavirus-positive cancer cells. Proc Natl Acad Sci U S A 2017;114(6):E990-E8. [DOI:10.1073/pnas.1615758114] [PMID] []
8. Narva SI, Seppänen MP, Raiko JR, Forsback SJ, Orte KJ, Virtanen JM, et al. Imaging of tumor hypoxia with 18F-EF5 PET/MRI in cervical cancer. Clin Nuc Med 2021;46(12):952-7. [DOI:10.1097/RLU.0000000000003914] [PMID]
9. Devarajan N, Manjunathan R, Ganesan SK. Tumor hypoxia: The major culprit behind cisplatin resistance in cancer patients. Crit Rev Oncol Hematol 2021;162:103327. [DOI:10.1016/j.critrevonc.2021.103327] [PMID]
10. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014;740:364-78. [DOI:10.1016/j.ejphar.2014.07.025] [PMID] []
11. Staedtke V, Roberts NJ, Bai R-Y, Zhou S. Clostridium novyi-NT in cancer therapy. Gen Dis 2016;3(2):144-52. [DOI:10.1016/j.gendis.2016.01.003] [PMID] []
12. Sharafabad BE, Abdoli A, Abdolmohammadi Khiav L, Meskini M, Jamur P, Dilmaghani A. Therapeutic Potential of Clostridium novyi-NT in Cancer: Current Knowledge and Future Perspectives. Curr Cancer Drug Targets 2023;23(9):682-96. [DOI:10.2174/1568009623666230413094253] [PMID]
13. Staedtke V, Bai R-Y, Sun W, Huang J, Kibler KK, Tyler BM, et al. Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats. Oncotarget 2015;6(8):5536. [DOI:10.18632/oncotarget.3627] [PMID] []
14. Krick EL, Sorenmo KU, Rankin SC, Cheong I, Kobrin B, Thornton K, et al. Evaluation of Clostridium novyi-NT spores in dogs with naturally occurring tumors. Am J Anim Vet Sci 2012;73(1):112-8. [DOI:10.2460/ajvr.73.1.112] [PMID] []
15. Janku F, Zhang HH, Pezeshki A, Goel S, Murthy R, Wang-Gillam A, et al. Intratumoral injection of Clostridium novyi-NT spores in patients with treatment-refractory advanced solid tumors. Clinl Cancer Res 2021;27(1):96-106. [DOI:10.1158/1078-0432.CCR-20-2065] [PMID]
16. Sharafabad BE, Abdoli A, Panahi M, Khiav LA, Jamur P, Jafari FA, et al. 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. Adv Pharmaceut Bull 2023;13(4):817. [DOI:10.34172/apb.2023.084] [PMID] []
17. Sears SM, Sharp CN, Krueger A, Oropilla GB, Saforo D, Doll MA, et al. C57BL/6 mice require a higher dose of cisplatin to induce renal fibrosis and CCL2 correlates with cisplatin-induced kidney injury. Am J Physiol Renal Physiol 2020;319(4):F674-F85. [DOI:10.1152/ajprenal.00196.2020] [PMID] []
18. Okunade KS. Human papillomavirus and cervical cancer. Obstet Gynecol 2020;40(5):602-8. [DOI:10.1080/01443615.2019.1634030] [PMID] []
19. Jalil AT, Karevskiy A. The cervical cancer (CC) epidemiology and human papillomavirus (HPV) in the middle east. Int J Env Eng Educ 2020;2(2):7-12. [DOI:10.55151/ijeedu.v2i2.29]
20. Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer 2019;18:1-15. [DOI:10.1186/s12943-019-1089-9] [PMID] []
21. Rashid M, Zadeh LR, Baradaran B, Molavi O, Ghesmati Z, Sabzichi M, et al. Up-down regulation of HIF-1α in cancer progression. Gene 2021;798:145796. [DOI:10.1016/j.gene.2021.145796] [PMID]
22. Federico C, Sun J, Muz B, Alhallak K, Cosper PF, Muhammad N, et al. Localized Delivery of Cisplatin to Cervical Cancer Improves Its Therapeutic Efficacy and Minimizes Its Side Effect Profile. Int J Radiat Oncol Biol Phys 2021;109(5):1483-94. [DOI:10.1016/j.ijrobp.2020.11.052] [PMID] []
23. Han Y, Kim B, Cho U, Park IS, Kim SI, Dhanasekaran DN, et al. Mitochondrial fission causes cisplatin resistance under hypoxic conditions via ROS in ovarian cancer cells. Oncogene 2019;38(45):7089-105. [DOI:10.1038/s41388-019-0949-5] [PMID]
24. Wang L, Wang Q, Tian X, Shi X. Learning from Clostridium novyi-NT: How to defeat cancer. J Cancer Res Therapeut 2018;14(Suppl 1). [DOI:10.4103/0973-1482.204841] [PMID]
25. Yaghoubi A, Ghazvini K, Khazaei M, Hasanian SM, Avan A, Soleimanpour S. The use of Clostridium in cancer therapy: a promising way. Rev Res Med Microb 2022;33(2):121-7. [DOI:10.1097/MRM.0000000000000281]
26. Dang LH, Bettegowda C, Agrawal N, Cheong I, Huso D, Frost P, et al. Targeting vascular and avascular compartments of tumors with C. novyi-NT and anti-microtubule agents. Cancer Biol Ther 2004;3(3):326-37. [DOI:10.4161/cbt.3.3.704] [PMID]
27. Janku F, Zhang HH, Pezeshki A, Goel S, Murthy R, Wang-Gillam A, et al. Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors. Clin Cancer Res 2021;27(1):96-106. [DOI:10.1158/1078-0432.CCR-20-2065] [PMID]
28. DeClue AE, Axiak-Bechtel SM, Zhang Y, Saha S, Zhang L, Tung D, et al. Immune response to C. novyi-NT immunotherapy. Vet Res 2018;49(1):38. [DOI:10.1186/s13567-018-0531-0] [PMID] []
29. Sharafabad BE, Abdoli A, Abdolmohammadi Khiav L, Meskini M, Jamur P, Dilmaghani A. Therapeutic Potential of Clostridium novyi-NT in Cancer: Current Knowledge and Future Perspectives. Curr Cancer Drug Targets 2023;23(9):682-96. [DOI:10.2174/1568009623666230413094253] [PMID]
30. Czabotar PE, Garcia-Saez AJ. Mechanisms of BCL-2 family proteins in mitochondrial apoptosis. Nat Rev Mol Cell Biol 2023;24(10):732-48. [DOI:10.1038/s41580-023-00629-4] [PMID]
31. Abou-Ghali M, Stiban J. Regulation of ceramide channel formation and disassembly: Insights on the initiation of apoptosis. Saudi J Biol Sci 2015;22(6):760-72. [DOI:10.1016/j.sjbs.2015.03.005] [PMID] []
32. Alizadeh J, da Silva Rosa SC, Weng X, Jacobs J, Lorzadeh S, Ravandi A, et al. Ceramides and ceramide synthases in cancer: Focus on apoptosis and autophagy. Eur J Cell Biol 2023;102(3):151337. [DOI:10.1016/j.ejcb.2023.151337] [PMID]
33. Albeituni S, Stiban J. Roles of Ceramides and Other Sphingolipids in Immune Cell Function and Inflammation. In: Honn KV, Zeldin DC, editors. The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases. Cham: Springer International Publishing; 2019. p. 169-91. [DOI:10.1007/978-3-030-21735-8_15] [PMID]

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