骨髓细胞疗法对1,2-二甲基肼（DMH）诱导的大鼠结肠癌的作用

Bone Marrow Cell Therapy on 1,2-Dimethylhydrazine (DMH)-Induced Colon Cancer in Rats.

作者信息

El-Khadragy Manal F, Nabil Heba M, Hassan Basmaa N, Tohamy Amany A, Waaer Hanaa F, Yehia Hany M, Alharbi Afra M, Moneim Ahmed Esmat Abdel

机构信息

Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia.

Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.

出版信息

Cell Physiol Biochem. 2018;45(3):1072-1083. doi: 10.1159/000487349. Epub 2018 Feb 7.

DOI:10.1159/000487349

PMID:29439258

Abstract

BACKGROUND/AIMS: Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats.

METHODS

The rats were randomly allocated into four groups: control, BMCs alone, DMH alone and BMCs with DMH. BMCs were injected intrarectally while DMH was injected subcutaneously at 20 mg/kg body weight once a week for 15 weeks. Histopathological examination and gene expression of survivin, β-catenin and multidrug resistance-1 (MDR-1) by real-time reverse transcription-polymerase chain reaction (RT-PCR) in rat colon tissues. This is in addition to oxidative stress markers in colon were performed across all groups.

RESULTS

The presence of aberrant crypt foci was reordered once histopathological examination of colon tissue from rats which received DMH alone. Administration of BMCs into rats starting from zero-day of DMH injection improved the histopathological picture which showed a clear improvement in mucosal layer, few inflammatory cells infiltration periglandular and in the lamina propria. Gene expression in rat colon tissue demonstrated that BMCs down-regulated survivin, β-catenin, MDR-1 and cytokeratin 20 genes expression in colon tissues after colon cancer induction. Amelioration of the colon status after administration of MSCs has been evidenced by a major reduction of lipid peroxidation, nitric oxide, and increasing of glutathione content and superoxide dismutase along with catalase activities.

CONCLUSION

Our findings demonstrated that BMCs have tumor suppressive effects in DMH-induced colon cancer as evidenced by down-regulation of survivin, β-catenin, and MDR-1 genes and enhancing the antioxidant activity.

摘要

背景/目的：基于干细胞的疗法因其在各种肿瘤治疗中可能发挥的作用而备受关注。骨髓干细胞被认为具有抗癌潜力，因其刺激免疫系统、迁移至肿瘤部位以及诱导癌细胞凋亡的能力而受到青睐。本研究旨在探讨骨髓细胞（BMCs）对1,2 - 二甲基肼（DMH）诱导的大鼠结肠癌的肿瘤抑制作用。

方法

将大鼠随机分为四组：对照组、单独注射BMCs组、单独注射DMH组和同时注射BMCs与DMH组。BMCs经直肠注射，而DMH以20 mg/kg体重皮下注射，每周一次，共15周。通过实时逆转录 - 聚合酶链反应（RT - PCR）对大鼠结肠组织进行组织病理学检查以及survivin、β - 连环蛋白和多药耐药 - 1（MDR - 1）基因表达检测。此外，还对所有组的结肠氧化应激标志物进行了检测。

结果

对单独接受DMH的大鼠结肠组织进行组织病理学检查时，发现存在异常隐窝灶。从DMH注射第0天开始给大鼠注射BMCs，改善了组织病理学表现，黏膜层有明显改善，腺周和固有层炎症细胞浸润较少。大鼠结肠组织中的基因表达表明，诱导结肠癌后，BMCs下调了结肠组织中survivin、β - 连环蛋白、MDR - 1和细胞角蛋白20基因的表达。给予间充质干细胞后结肠状态的改善表现为脂质过氧化、一氧化氮显著减少，谷胱甘肽含量、超氧化物歧化酶以及过氧化氢酶活性增加。