Rezai Shaghayegh, Ghorbani Elnaz, Nazari Seyedeh Elnaz, Rahmani Farzad, Hassanian Seyed Mahdi, Afshari Asma, Habibi Najafi Mohammad Bagher, Avan Amir, Ryzhikov Mikhail, Soleimanpour Saman, Khazei Majid
Department of Medical Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Med Sci. 2025 Apr 1;50(4):247-259. doi: 10.30476/ijms.2024.102396.3530. eCollection 2025 Apr.
Colorectal cancer (CRC) is a serious health problem, and finding new treatments is important. There is growing evidence for the antitumor activity of probiotics. This study investigated the anti-cancer potential of a probiotic mix containing , , , and , alone or in combination with the chemotherapy drug 5-fluorouracil, against CRC.
The research was carried out in Mashhad in 2021. The cytotoxic effect of Lactobacillus isolates on CRC cells was investigated in two-dimensional and three-dimensional cell culture models. Histological staining and molecular approaches were used to investigate the regulatory mechanism of Lactobacillus isolates on cell migration, inflammation, fibrosis, cell cycle progression, apoptosis, and tumor necrosis in the CRC mouse model. Statistical analysis was performed using SPSS software version 20 with a significance level of P<0.05. The tests employed included the Kolmogorov-Smirnov, ANOVA, Dunnett's , and Kruskal-Wallis.
Lactobacillus strains effectively suppressed tumor growth in CRC by promoting cell death and inhibiting fibrosis and inflammation. These bacteria regulated apoptosis-related genes such as Bcl-2-associated protein x (P=0.0033), and (P=0.0029), leading to increased tumor necrosis. Treatment with bacterial supernatants reduced tumor size and fibrosis by downregulating collagen type I, alpha 1 () (P=0.024), (P=0.0231), and (P=0.0466), and transforming growth factor-beta expression. Additionally, they suppressed inflammation by decreasing tumor necrosis factor-alpha (P=0.0001), interleukin 6, and IL-1β (P=0.0198) levels in tumor tissues. Furthermore, the treatment inhibited CRC cell migration by modulating epithelial cadherin (P=0.0198) and matrix metallopeptidase 2 (P=0.033) expression.
Findings indicated that co-administration of Lactobacillus isolates with 5-FU could improve the anti-tumor properties of the standard drug, 5-FU, supporting the therapeutic potential of these safe isolated lactic acid bacteria for CRC patients .
结直肠癌（CRC）是一个严重的健康问题，寻找新的治疗方法很重要。越来越多的证据表明益生菌具有抗肿瘤活性。本研究调查了一种含有嗜酸乳杆菌、植物乳杆菌、干酪乳杆菌和鼠李糖乳杆菌的益生菌混合物单独使用或与化疗药物5-氟尿嘧啶联合使用对结直肠癌的抗癌潜力。
该研究于2021年在马什哈德进行。在二维和三维细胞培养模型中研究了乳酸杆菌分离株对结直肠癌细胞的细胞毒性作用。在结直肠癌小鼠模型中，采用组织学染色和分子方法研究乳酸杆菌分离株对细胞迁移、炎症、纤维化、细胞周期进程、凋亡和肿瘤坏死的调节机制。使用SPSS 20.0软件进行统计分析，显著性水平为P<0.05。所采用的检验包括Kolmogorov-Smirnov检验、方差分析、Dunnett检验和Kruskal-Wallis检验。
乳酸杆菌菌株通过促进细胞死亡以及抑制纤维化和炎症，有效抑制了结直肠癌中的肿瘤生长。这些细菌调节了与凋亡相关的基因，如Bcl-2相关蛋白x（P=0.0033）和半胱天冬酶3（P=0.0029），导致肿瘤坏死增加。用细菌上清液处理可通过下调I型胶原蛋白α1（P=0.024）、α2（P=0.0231）和α5（P=0.0466）以及转化生长因子-β的表达来减小肿瘤大小和减轻纤维化。此外，它们通过降低肿瘤组织中肿瘤坏死因子-α（P=0.0001）、白细胞介素6和白细胞介素1β（P=0.0198）的水平来抑制炎症。此外，该处理通过调节上皮钙黏蛋白（P=0.0198）和基质金属肽酶2（P=0.033）的表达来抑制结直肠癌细胞迁移。
研究结果表明，将乳酸杆菌分离株与5-氟尿嘧啶联合使用可以提高标准药物5-氟尿嘧啶的抗肿瘤特性，支持这些安全的分离乳酸菌对结直肠癌患者的治疗潜力。
