Tsapieva Anna N, Chernov Alexander N, Duplik Nadezhda V, Morozova Anastasiya O, Filatenkova Tatiana A, Suvorova Mariia A, Egidarova Elena, Galimova Elvira S, Bogatireva Kseniya, Suvorov Alexander N
Scientific 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, Russia.
Department of Biological Chemistry, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg, State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia.
Microorganisms. 2025 Jan 3;13(1):76. doi: 10.3390/microorganisms13010076.
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 (GAS) strains for tumor treatment. This study aimed to investigate the oncolytic efficacy of GUR and its M protein knockout mutant, strain GURSA1, which was genetically constructed to minimize overall toxicity, against mouse hepatoma 22A, pancreatic cancer PANC02, and human glioma U251 cells, both and , using the C57BL/6 mouse model.
The 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 oncolytic effect of GAS strains. Statistical analysis was conducted using Student's -test and Mann-Whitney U-test with GraphPad Prism software.
The model showed that the live 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 GURSA1 strain demonstrated strong (86.5 ± 1.6%) and moderate (36.5 ± 1.8%) oncolytic activities against glioma and hepatoma cells. Additionally, the GURSA1 strain did not exhibit cytotoxic activity against healthy skin fibroblast cells (cell viability 104.2 ± 1.3%, 0.2542). We demonstrated that tumor treatment with GURSA1 significantly increased the lifespan of C57BL/6 mice with hepatoma (34 days, 0.040) and pancreatic cancer (32 days, 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.
Both GUR and GURSA1 strains demonstrated strong oncolytic activity against murine hepatoma 22a, pancreatic cancer PANC02, and human U251 glioma cells . In contrast, GUR and GURSA1 did not show toxicity against human normal skin fibroblasts. The overall survival rate and lifespan of mice treated with GURSA1, a strain lacking the M protein on its surface, were significantly higher compared to the control and GUR strain groups.
癌症仍是全球主要的死亡原因。包括放疗和化疗在内的传统治疗方式往往难以实现完全缓解，这凸显了对新型治疗策略的迫切需求。一种有前景的方法涉及A组链球菌（GAS）菌株对肿瘤治疗的溶瘤潜力。本研究旨在使用C57BL/6小鼠模型，研究GUR及其M蛋白敲除突变体GURSA1菌株（通过基因构建以尽量减少总体毒性）对小鼠肝癌22A、胰腺癌PANC02和人胶质瘤U251细胞的溶瘤效果。
使用MTT法和实时xCELLigence系统研究GAS菌株对人胶质瘤U251、胰腺癌PANC02、小鼠肝癌22a和正常皮肤成纤维细胞的溶瘤细胞毒性活性。使用肝癌和胰腺癌的同基因小鼠模型评估GAS菌株的溶瘤效果。使用GraphPad Prism软件进行Student's t检验和Mann-Whitney U检验进行统计分析。
模型显示，活的GUR菌株对胰腺癌PANC02细胞具有强烈的细胞毒性作用（67.4±1.9%）。该菌株对胶质瘤和肝癌细胞分别表现出中度（38.0±1.8%）和弱（16.3±5.4%）的溶瘤活性。相比之下，GURSA1菌株对胶质瘤和肝癌细胞表现出强烈（86.5±1.6%）和中度（36.5±1.8%）的溶瘤活性。此外，GURSA1菌株对健康皮肤成纤维细胞未表现出细胞毒性活性（细胞活力为104.2±1.3%，P=0.2542）。我们证明，与对照组（分别为24天和28天）相比，用GURSA1治疗肿瘤可显著延长C57BL/6肝癌小鼠（34天，P=0.040）和胰腺癌小鼠（32天，P=0.039）的寿命。寿命延长伴随着肿瘤进展的减缓，这在小鼠接受GAS菌株治疗时肝癌和胰腺癌肿瘤生长的减少中得到证明。
GUR和GURSA1菌株对小鼠肝癌22a、胰腺癌PANC02和人U251胶质瘤细胞均表现出强烈的溶瘤活性。相比之下，GUR和GURSA1对人正常皮肤成纤维细胞未显示毒性。与对照组和GUR菌株组相比，表面缺乏M蛋白的GURSA1菌株治疗的小鼠的总生存率和寿命显著更高。
