益生菌（嗜酸乳杆菌、鼠李糖乳杆菌 GG）和塞来昔布的预防性干预可调节 1,2-二甲基肼诱导的实验性结肠癌变中 Bax 介导的细胞凋亡。

Prophylactic intervention of probiotics (L.acidophilus, L.rhamnosus GG) and celecoxib modulate Bax-mediated apoptosis in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis.

机构信息

Department of Microbiology, Basic Medical Sciences (Block I), South Campus, Panjab University, -160014, Chandigarh, India.

出版信息

BMC Cancer. 2018 Nov 13;18(1):1111. doi: 10.1186/s12885-018-4999-9.

BACKGROUND

Colorectal cancer has been found to be attenuated either with prophylactic manipulation of gut microbiome with probiotics or celecoxib, a non-steroidal anti-inflammatory drug mainly by suppressing early pro-carcinogenic markers in various experimental studies. Therefore, the present study was designed to assess the prophylactic potential of combinatorial administration of probiotics (Lactobacillus rhamnosus GG, Lactobacillus acidophilus) and celecoxib in experimental colon carcinogenesis.

METHODS

Six groups of Spraugue Dawely rats received probiotics L.rhamnosus GG or/and L.acidophilus in combination with celecoxib one week prior to the inducement of tumor by 1,2-dimethylhydrazine (DMH) and the treatment continued for 18 weeks. Prophylactic potentials of probiotics and celecoxib were determined by employing various methods such as tumor incidence, tumor burden, tumor multiplicity, apoptosis, caspase activity, expression of proto-oncogene K-ras and tumor suppressor p53 gene in colonic tumors.

RESULTS

Interestingly, it was found that one week prior supplementation of both probiotics and celecoxib reduced tumor burden, tumor multiplicity, down-regulated the expression of anti-apoptotic Bcl-2, proto-oncogene K-ras and up-regulated pro-apoptotic Bax as well as tumor suppressor p53 in L.rhamnosus GG + celecoxib+DMH animals compared with counter controls and DMH-treated.

CONCLUSIONS

It can be concluded that such combinatorial approach may be useful in reducing the burden and severity of disease in highly susceptible individuals but needs to be validated clinically.

背景

在各种实验研究中，通过抑制早期促癌标志物，已经发现预防性地操纵肠道微生物组与益生菌或塞来昔布（一种主要通过抑制早期促癌标志物的非甾体抗炎药）可减轻结直肠癌的发生。因此，本研究旨在评估益生菌（鼠李糖乳杆菌 GG、嗜酸乳杆菌）和塞来昔布联合给药在实验性结肠癌发生中的预防潜力。

方法

六组 Spraugue Dawely 大鼠在肿瘤诱导前一周接受益生菌 L.rhamnosus GG 或/和 L.acidophilus 联合塞来昔布治疗，并在 1,2-二甲基肼（DMH）诱导后继续治疗 18 周。通过各种方法，如肿瘤发生率、肿瘤负担、肿瘤多发性、细胞凋亡、半胱天冬酶活性、结肠肿瘤中原癌基因 K-ras 和肿瘤抑制基因 p53 基因的表达，来确定益生菌和塞来昔布的预防潜力。