Department of Bio-Health Convergence Major, Duksung Women's University, Seoul 01369, Korea.
Department of Pharmacy, Duksung Women's University, Seoul 01369, Korea.
Int J Mol Sci. 2022 Aug 29;23(17):9788. doi: 10.3390/ijms23179788.
Paraprobiotics, inactivated microbial cells, regulate immune system and exhibit antioxidant and anti-inflammatory activities in patients with weakened immunity or the elderly. This study evaluated the anti-tumor effects of heat-killed and on human gastric cancer MKN1 cells in vitro and in vivo in xenograft animal models. First, cytotoxicity and apoptosis in MKN1 cells of 11 different heat-killed or strains were examined using the MTT assay or flow cytometry, respectively. Then, BALB/c nude mice xenograft animal models were implanted with human gastric cancer MKN1 cells and orally administered a selected single or a mixture of heat-killed bacterial strains to investigate their inhibitory effect on tumor growth. In addition, the expression of p-Akt, p53, Bax, Bak, cleaved caspase-9, -3, and PARP in the tumor tissues was analyzed using Western blotting assay or immunohistochemistry staining. The results show that heat-killed MG731 (MG731), MG5346 (MG5346), and MG5200 (MG5200) induced relatively greater apoptosis than other strains in MKN1 cells. Oral administration of a single dose or a mixture of MG731, MG5346, or MG5200 significantly delayed tumor growth, and MG731 had the most effective anti-tumor effect in the xenograft model. Protein expression of p-Akt, p53, Bax, cleaved caspase-3 and -9, and PARP in tumors derived from the xenograft model correlated with the results of the immunohistochemistry staining.
益生菌，即已失活的微生物细胞，可调节免疫系统，并具有抗氧化和抗炎活性，适用于免疫功能低下或老年患者。本研究评估了热灭活 11 株 和 对体外培养的人胃癌 MKN1 细胞和异种移植动物模型的体内抗肿瘤作用。首先，通过 MTT 检测或流式细胞术分别检测 11 株不同热灭活 或 菌株对 MKN1 细胞的细胞毒性和凋亡作用。然后，将人胃癌 MKN1 细胞接种于 BALB/c 裸鼠异种移植动物模型，并口服给予选定的单一或混合热灭活细菌菌株，以研究其对肿瘤生长的抑制作用。此外，还通过 Western blot 检测或免疫组化染色分析肿瘤组织中 p-Akt、p53、Bax、Bak、cleaved caspase-9、-3 和 PARP 的表达。结果表明，热灭活的 MG731（MG731）、MG5346（MG5346）和 MG5200（MG5200）在 MKN1 细胞中诱导的凋亡作用明显大于其他菌株。单次口服或混合给予 MG731、MG5346 或 MG5200 可显著延缓肿瘤生长，且 MG731 在异种移植模型中具有最有效的抗肿瘤作用。肿瘤组织中 p-Akt、p53、Bax、cleaved caspase-3 和 -9 以及 PARP 的蛋白表达与免疫组化染色结果相关。
