鼠结直肠癌变中，罗伊氏乳杆菌 ATCC7469 胞外多糖与低剂量电离辐射协同作用，调节信号分子靶点。
Lactobacillus rhamnosus ATCC 7469 exopolysaccharides synergizes with low level ionizing radiation to modulate signaling molecular targets in colorectal carcinogenesis in rats.
机构信息
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Radiation Microbiology Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
出版信息
Biomed Pharmacother. 2017 Aug;92:384-393. doi: 10.1016/j.biopha.2017.05.089. Epub 2017 May 26.
Combination therapy that targets cellular signaling pathway represents an alternative therapy for the treatment of colon cancer (CRC). The present study was therefore aimed to investigate the probable interaction of Lactobacillus rhamnosus ATCC 7469 exopolysaccharides (EPS) with low level ionizing γ radiation (γ-R) exposure against dimethylhydrazine (DMH)- induced colorectal carcinogenesis in rats. Colon cancer was induced with 20mg DMH/kg BW. Rats received daily by gastric gavage 100mg EPS/Kg BW concomitant with 1Gy γ-R over two months. Colonic oxidative and inflammatory stresses were assessed. The change in the expression of p-p38 MAPK, p-STAT3, β-catenin, NF-kB, COX-2 and iNOS was evaluated by western blotting and q-PCR. It was found that DMH treatment significantly induced colon oxidative injury accompanied by inflammatory disturbance along with increased protein expression of the targeted signaling factors p-p38 MAPK, p-STAT3 and β-catenin. The mRNA gene expression of NF-kB, COX-2 and iNOS was significantly higher in DMH-treated animals. It's worthy to note that colon tissues with DMH treatment showed significant dysplasia and anaplasia of the glandular mucosal lining epithelium with loses of goblet cells formation, pleomorphism in the cells and hyperchromachia in nuclei. Interestingly, EPS treatment with γ-R exposure showed statistically significant amelioration of the oxidative and inflammatory biomarkers with modulated signaling molecular factors accompanied by improved histological structure against DMH-induced CRC. In conclusion, our findings showed that Lactobacillus rhamnosus ATCC 7469 EPS with low level γ-R in synergistic interaction are efficacious control against CRC progression throughout the modulation of key signaling growth factors associated with inflammation via antioxidant mediated anti-inflammatory and anti-proliferative activities.
联合针对细胞信号通路的治疗方法代表了治疗结肠癌（CRC）的另一种治疗方法。因此，本研究旨在探讨鼠李糖乳杆菌 ATCC 7469 胞外多糖（EPS）与低剂量电离γ 射线（γ-R）暴露对二甲基肼（DMH）诱导的大鼠结直肠癌变的可能相互作用。采用 20mg DMH/kg BW 诱导结肠癌。大鼠连续两个月每天经胃管灌胃 100mg EPS/Kg BW，同时接受 1Gy γ-R 照射。评估结肠氧化和炎症应激。通过 Western blot 和 q-PCR 评估 p-p38 MAPK、p-STAT3、β-catenin、NF-kB、COX-2 和 iNOS 的表达变化。结果发现，DMH 处理显著诱导了结肠氧化损伤，同时伴有炎症紊乱，以及靶向信号因子 p-p38 MAPK、p-STAT3 和β-catenin 的蛋白表达增加。DMH 处理动物的 NF-kB、COX-2 和 iNOS 的 mRNA 基因表达显著升高。值得注意的是，DMH 处理的结肠组织显示出腺粘膜衬里上皮的明显异型增生和发育不良，杯状细胞形成丧失，细胞多形性和核深染。有趣的是，EPS 联合 γ-R 暴露治疗显示出对氧化和炎症生物标志物的统计学显著改善，同时调节了信号分子因子，改善了组织学结构，防止了 DMH 诱导的 CRC。总之，我们的研究结果表明，鼠李糖乳杆菌 ATCC 7469 EPS 与低剂量γ-R 的协同作用，通过抗氧化介导的抗炎和抗增殖活性，对与炎症相关的关键信号生长因子进行调节，是防治 CRC 进展的有效方法。
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