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The anti-tumour effect of induced pluripotent stem cells against submandibular gland carcinoma in rats is achieved via modulation of the apoptotic response and the expression of Sirt-1, TGF-β, and MALAT-1 in cancer cells.
Molecular and Cellular Biochemistry ( IF 3.5 ) Pub Date : 2021-09-17 , DOI: 10.1007/s11010-021-04255-6
Eman Mohamed Faruk 1, 2 , Dina Sabry 3, 4 , Ahmed A Morsi 5 , Yasmine Alaa El-Din 6 , Neama M Taha 7 , Engy Medhat 3
Affiliation  

The era of induced pluripotent stem cells (iPSCs) was used as novel biotechnology to replace embryonic stem cells bypassing the ethical concerns and problems of stem cell transplant rejection. The anti-tumour potential of iPSCs against many tumours including salivary cancer was proven in previous studies. The current study aimed to investigate the contribution of the Bax, Sirt-1, TGF-β, and MALAT genes and/or their protein expression to the pathogenesis of submandibular carcinogenesis before and after iPSCs treatment. Thirty Wistar albino rats were equally assigned into three groups: group I (control), group II (Squamous cell carcinoma (SCC)): submandibular glands were injected SCC cells, and group III (SCC/iPSCs): SCC rats were treated by 5 × 106 iPSCs. Submandibular gland sections were subjected to histological and immunohistochemical analyses to detect mucopolysaccharides, Bax, and TGF-β expression as well as PCR quantification for TGF-β, Sirt-1, and lncRNA MALAT-1 gene expressions. Western blotting was also used to detect Sirt-1 and TGF-β protein expressions. SCC group revealed infiltration by sheets of malignant squamous cells with or without keratin pearls and inflammatory cells, in addition to upregulation of TGF-β, Sirt-1, MALAT-1, and Bax, whereas SCC/iPSCs group showed an improved submandibular histoarchitecture with the maintenance of the secretory function. Bax and TGF-β immunoexpression were significantly reduced. The upregulated TGF-β, Sirt-1, and MALAT-1 genes were significantly decreased. iPSCs protected against the experimentally induced submandibular gland carcinoma that might be achieved via their regenerative potential and their regulatory modulation of Sirt-1, TGF-β, and MALAT-1 gene/protein expressions and of the apoptotic response in cancer cells.

中文翻译:

诱导多能干细胞对大鼠颌下腺癌的抗肿瘤作用是通过调节癌细胞中的凋亡反应和Sirt-1、TGF-β和MALAT-1的表达来实现的。

诱导多能干细胞 (iPSC) 时代被用作替代胚胎干细胞的新型生物技术,从而绕过了伦理问题和干细胞移植排斥问题。iPSCs 对包括唾液癌在内的许多肿瘤的抗肿瘤潜力已在先前的研究中得到证实。本研究旨在探讨 Bax、Sirt-1、TGF-β 和 MALAT 基因和/或它们的蛋白表达对 iPSCs 治疗前后下颌下癌发病机制的贡献。30 只 Wistar 白化病大鼠平均分为三组:I 组(对照组)、II 组(鳞状细胞癌 (SCC)):下颌下腺注射 SCC 细胞,III 组(SCC/iPSCs):SCC 大鼠接受 5 × 106 个 iPSC。对颌下腺切片进行组织学和免疫组织化学分析以检测粘多糖、Bax 和 TGF-β 的表达,以及对 TGF-β、Sirt-1 和 lncRNA MALAT-1 基因表达的 PCR 定量。Western印迹也用于检测Sirt-1和TGF-β蛋白表达。SCC 组除了 TGF-β、Sirt-1、MALAT-1 和 Bax 上调外,还显示出有或没有角蛋白珠和炎性细胞的恶性鳞状细胞片浸润,而 SCC/iPSCs 组显示下颌下组织结构改善维持分泌功能。Bax 和 TGF-β 免疫表达显着降低。上调的 TGF-β、Sirt-1 和 MALAT-1 基因显着降低。
更新日期:2021-09-17
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