Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chang Gung Children's Hospital, 12L, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan 333, Taiwan, ROC.
Br J Nutr. 2012 Jun;107(11):1623-34. doi: 10.1017/S0007114511004934. Epub 2011 Sep 30.
Modulation of the cellular response by the administration of probiotic bacteria may be an effective strategy for preventing or inhibiting tumour growth. We orally pre-inoculated mice with probiotics Lactobacillus acidophilus NCFM (La) for 14 d. Subcutaneous dorsal-flank tumours and segmental orthotopic colon cancers were implanted into mice using CT-26 murine colon adenocarcinoma cells. On day 28 after tumour initiation, the lamina propria of the colon, mesenteric lymph nodes (MLN) and spleen were harvested and purified for flow cytometry and mRNA analyses. We demonstrated that La pre-inoculation reduced tumour volume growth by 50·3 %, compared with untreated mice at 28 d after tumour implants (2465·5 (SEM 1290·4) v. 4950·9 (SEM 1689·3) mm³, P<0·001). Inoculation with La reduced the severity of colonic carcinogenesis caused by CT-26 cells, such as level of colonic involvement and structural abnormality of epithelial/crypt damage. Moreover, La enhanced apoptosis of CT-26 cells both in dorsal-flank tumour and segmental orthotopic colon cancer, and the mean counts of apoptotic body were higher in mice pre-inoculated with La (P<0·05) compared with untreated mice. La pre-inoculation down-regulated the CXCR4 mRNA expressions in the colon, MLN and extra-intestinal tissue, compared with untreated mice (P<0·05). In addition, La pre-inoculation reduced the mean fluorescence index of MHC class I (H-2Dd, -Kd and -Ld) in flow cytometry analysis. Taken together, these findings suggest that probiotics La may play a role in attenuating tumour growth during CT-26 cell carcinogenesis. The down-regulated expression of CXCR4 mRNA and MHC class I, as well as increasing apoptosis in tumour tissue, indicated that La may be associated with modulating the cellular response triggered by colon carcinogenesis.
通过给予益生菌来调节细胞反应可能是预防或抑制肿瘤生长的有效策略。我们用嗜酸乳杆菌 NCFM(La)对小鼠进行了 14 天的口服预接种。使用 CT-26 结肠腺癌细胞将皮下背部侧翼肿瘤和节段性原位结肠肿瘤植入小鼠体内。在肿瘤起始后 28 天,收获并纯化结肠固有层、肠系膜淋巴结(MLN)和脾脏,进行流式细胞术和 mRNA 分析。我们证明,与未处理的肿瘤植入后 28 天的小鼠相比,La 预接种将肿瘤体积生长减少了 50.3%(2465.5(SEM 1290.4)v. 4950.9(SEM 1689.3)mm³,P<0.001)。La 接种降低了 CT-26 细胞引起的结肠癌变的严重程度,例如结肠受累程度和上皮/隐窝损伤的结构异常。此外,La 增强了 CT-26 细胞在背部侧翼肿瘤和节段性原位结肠肿瘤中的凋亡,并且与未处理的小鼠相比,预先接种 La 的小鼠中的凋亡体的平均计数更高(P<0.05)。与未处理的小鼠相比,La 预接种降低了结肠、MLN 和肠外组织中 CXCR4 mRNA 的表达(P<0.05)。此外,La 预接种降低了流式细胞术分析中 MHC Ⅰ类(H-2Dd、-Kd 和 -Ld)的平均荧光指数。综上所述,这些发现表明益生菌 La 可能在 CT-26 细胞癌变过程中发挥作用,从而减弱肿瘤生长。CXCR4 mRNA 和 MHC Ⅰ类的下调表达以及肿瘤组织中凋亡的增加表明,La 可能与调节由结肠癌变引发的细胞反应有关。