Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i>
Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic...
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2025-01-01
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| author | Anna N. Tsapieva Alexander N. Chernov Nadezhda V. Duplik Anastasiya O. Morozova Tatiana A. Filatenkova Mariia A. Suvorova Elena Egidarova Elvira S. Galimova Kseniya Bogatireva Alexander N. Suvorov |
| author_facet | Anna N. Tsapieva Alexander N. Chernov Nadezhda V. Duplik Anastasiya O. Morozova Tatiana A. Filatenkova Mariia A. Suvorova Elena Egidarova Elvira S. Galimova Kseniya Bogatireva Alexander N. Suvorov |
| author_sort | Anna N. Tsapieva |
| collection | DOAJ |
| description | Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A <i>Streptococcus</i> (GAS) strains for tumor treatment. This study aimed to investigate the oncolytic efficacy of <i>S. pyogenes</i> GUR and its M protein knockout mutant, <i>S. pyogenes</i> strain GURSA1, which was genetically constructed to minimize overall toxicity, against mouse hepatoma 22A, pancreatic cancer PANC02, and human glioma U251 cells, both <i>in vitro</i> and <i>in vivo</i>, using the C57BL/6 mouse model. Methods: The <i>in vitro</i> oncolytic cytotoxic activity of GAS strains was studied against human glioma U251, pancreatic cancer PANC02, murine hepatoma 22a, and normal skin fibroblast cells using the MTT assay and the real-time xCELLigence system. A syngeneic mouse model of hepatoma and pancreatic cancer was used to evaluate the <i>in vivo</i> oncolytic effect of GAS strains. Statistical analysis was conducted using Student’s <i>t</i>-test and Mann–Whitney U-test with GraphPad Prism software. Results: The <i>in vitro</i> model showed that the live <i>S. pyogenes</i> GUR strain had a strong cytotoxic effect (67.4 ± 1.9%) against pancreatic cancer PANC02 cells. This strain exhibited moderate (38.0 ± 1.8%) and weak (16.3 ± 5.4%) oncolytic activities against glioma and hepatoma cells, respectively. In contrast, the <i>S. pyogenes</i> GURSA1 strain demonstrated strong (86.5 ± 1.6%) and moderate (36.5 ± 1.8%) oncolytic activities against glioma and hepatoma cells. Additionally, the <i>S. pyogenes</i> GURSA1 strain did not exhibit cytotoxic activity against healthy skin fibroblast cells (cell viability 104.2 ± 1.3%, <i>p =</i> 0.2542). We demonstrated that tumor treatment with <i>S. pyogenes</i> GURSA1 significantly increased the lifespan of C57BL/6 mice with hepatoma (34 days, <i>p =</i> 0.040) and pancreatic cancer (32 days, <i>p =</i> 0.039) relative to the control groups (24 and 28 days, respectively). Increased lifespan was accompanied by a slowdown in tumor progression, as evidenced by a reduction in the growth of hepatoma and pancreatic cancer tumors under treatment with GAS strains in mice. Conclusions: Both <i>S. pyogenes</i> GUR and <i>S. pyogenes</i> GURSA1 strains demonstrated strong oncolytic activity against murine hepatoma 22a, pancreatic cancer PANC02, and human U251 glioma cells <i>in vitro</i>. In contrast, <i>S. pyogenes</i> GUR and GURSA1 did not show toxicity against human normal skin fibroblasts. The overall survival rate and lifespan of mice treated with <i>S. pyogenes</i> GURSA1, a strain lacking the M protein on its surface, were significantly higher compared to the control and <i>S. pyogenes</i> GUR strain groups. |
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| institution | Kabale University |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-578a8419eb244fdd82926998c1af427d2025-01-24T13:42:33ZengMDPI AGMicroorganisms2076-26072025-01-011317610.3390/microorganisms13010076Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i>Anna N. Tsapieva0Alexander N. Chernov1Nadezhda V. Duplik2Anastasiya O. Morozova3Tatiana A. Filatenkova4Mariia A. Suvorova5Elena Egidarova6Elvira S. Galimova7Kseniya Bogatireva8Alexander N. Suvorov9Scientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaDepartment of Biotechnology and Biomedicine, Disease Systems Immunology, Technical University of Denmark, Søltofts Plads 224, 2800 Kongens Lyngby, DenmarkScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaScientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, RussiaBackground: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A <i>Streptococcus</i> (GAS) strains for tumor treatment. This study aimed to investigate the oncolytic efficacy of <i>S. pyogenes</i> GUR and its M protein knockout mutant, <i>S. pyogenes</i> strain GURSA1, which was genetically constructed to minimize overall toxicity, against mouse hepatoma 22A, pancreatic cancer PANC02, and human glioma U251 cells, both <i>in vitro</i> and <i>in vivo</i>, using the C57BL/6 mouse model. Methods: The <i>in vitro</i> oncolytic cytotoxic activity of GAS strains was studied against human glioma U251, pancreatic cancer PANC02, murine hepatoma 22a, and normal skin fibroblast cells using the MTT assay and the real-time xCELLigence system. A syngeneic mouse model of hepatoma and pancreatic cancer was used to evaluate the <i>in vivo</i> oncolytic effect of GAS strains. Statistical analysis was conducted using Student’s <i>t</i>-test and Mann–Whitney U-test with GraphPad Prism software. Results: The <i>in vitro</i> model showed that the live <i>S. pyogenes</i> GUR strain had a strong cytotoxic effect (67.4 ± 1.9%) against pancreatic cancer PANC02 cells. This strain exhibited moderate (38.0 ± 1.8%) and weak (16.3 ± 5.4%) oncolytic activities against glioma and hepatoma cells, respectively. In contrast, the <i>S. pyogenes</i> GURSA1 strain demonstrated strong (86.5 ± 1.6%) and moderate (36.5 ± 1.8%) oncolytic activities against glioma and hepatoma cells. Additionally, the <i>S. pyogenes</i> GURSA1 strain did not exhibit cytotoxic activity against healthy skin fibroblast cells (cell viability 104.2 ± 1.3%, <i>p =</i> 0.2542). We demonstrated that tumor treatment with <i>S. pyogenes</i> GURSA1 significantly increased the lifespan of C57BL/6 mice with hepatoma (34 days, <i>p =</i> 0.040) and pancreatic cancer (32 days, <i>p =</i> 0.039) relative to the control groups (24 and 28 days, respectively). Increased lifespan was accompanied by a slowdown in tumor progression, as evidenced by a reduction in the growth of hepatoma and pancreatic cancer tumors under treatment with GAS strains in mice. Conclusions: Both <i>S. pyogenes</i> GUR and <i>S. pyogenes</i> GURSA1 strains demonstrated strong oncolytic activity against murine hepatoma 22a, pancreatic cancer PANC02, and human U251 glioma cells <i>in vitro</i>. In contrast, <i>S. pyogenes</i> GUR and GURSA1 did not show toxicity against human normal skin fibroblasts. The overall survival rate and lifespan of mice treated with <i>S. pyogenes</i> GURSA1, a strain lacking the M protein on its surface, were significantly higher compared to the control and <i>S. pyogenes</i> GUR strain groups.https://www.mdpi.com/2076-2607/13/1/76<i>Streptococcus pyogenes</i>recombinant M proteinhuman glioma U251pancreatic cancer PANC02mice hepatoma 22acytotoxicity |
| spellingShingle | Anna N. Tsapieva Alexander N. Chernov Nadezhda V. Duplik Anastasiya O. Morozova Tatiana A. Filatenkova Mariia A. Suvorova Elena Egidarova Elvira S. Galimova Kseniya Bogatireva Alexander N. Suvorov Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i> Microorganisms <i>Streptococcus pyogenes</i> recombinant M protein human glioma U251 pancreatic cancer PANC02 mice hepatoma 22a cytotoxicity |
| title | Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i> |
| title_full | Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i> |
| title_fullStr | Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i> |
| title_full_unstemmed | Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i> |
| title_short | Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i> |
| title_sort | studying the oncolytic activity of i streptococcus pyogenes i strains against hepatoma glioma and pancreatic cancer i in vitro i and i in vivo i |
| topic | <i>Streptococcus pyogenes</i> recombinant M protein human glioma U251 pancreatic cancer PANC02 mice hepatoma 22a cytotoxicity |
| url | https://www.mdpi.com/2076-2607/13/1/76 |
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