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The influence of conjugated linoleic acid on the expression of peroxisome proliferator-activated receptor-γ and selected apoptotic genes in non-small cell lung cancer.
Molecular and Cellular Biochemistry ( IF 3.5 ) Pub Date : 2020-01-29 , DOI: 10.1007/s11010-020-03689-8
Bartosz Kazimierz Słowikowski 1 , Hanna Drzewiecka 1 , Michał Malesza 1 , Ida Mądry 1 , Karolina Sterzyńska 2 , Paweł Piotr Jagodziński 1
Affiliation  

In recent years, peroxisome proliferator-activated receptor-γ (PPARγ) has been intensively studied. Because its activation is often associated with changes in the expression level of various apoptotic genes, many studies have emphasized the role of PPARγ as an important anticancer agent. However, in different types of cancer, different genes are influenced by PPARγ action. Previous studies showed that conjugated linoleic acid (CLA) was able to induce apoptosis, upregulate PPARG gene expression and activate PPARγ protein in certain human cancer cell lines. Moreover, some PPARγ agonists inhibited the growth of human lung cancer cells through the induction of apoptosis. Nevertheless, the impact of CLA on PPARγ mRNA and protein levels in non-small cell lung cancer (NSCLC) cell lines has not been investigated thus far. Therefore, in our study, we analysed the influence of the c9,t11 linoleic acid isomer on the expression of PPARG and other genes involved in the apoptotic response (BCL-2, BAX, and CDKN1A) in two NSCLC cell lines of different histological origin (A549 and Calu-1) and in normal human bronchial epithelial Beas-2B cells. Cells were treated with several doses of c9,t11 CLA, followed by RNA and protein isolation, cDNA synthesis, real-time quantitative PCR (RT-qPCR) and Western blot analysis. We showed that the investigated CLA isomer was able to enhance the expression of PPARγ in the examined cell lines and alter the mRNA and protein levels of genes involved in apoptosis. Fluorescent staining and MMT assay revealed the antiproliferative potential of CLA as well as its ability to activate pathways that lead to cell death.

中文翻译:

共轭亚油酸对非小细胞肺癌过氧化物酶体增殖物激活受体-γ和选择性凋亡基因表达的影响。

近年来,过氧化物酶体增殖物激活受体-γ(PPARγ)得到了深入研究。由于其激活往往与各种凋亡基因表达水平的变化有关,因此许多研究强调了 PPARγ 作为重要抗癌剂的作用。然而,在不同类型的癌症中,不同的基因受到 PPARγ 作用的影响。先前的研究表明,共轭亚油酸 (CLA) 能够在某些人类癌细胞系中诱导细胞凋亡、上调 PPARG 基因表达并激活 PPARγ 蛋白。此外,一些PPARγ激动剂通过诱导细胞凋亡来抑制人肺癌细胞的生长。然而,迄今为止,CLA 对非小细胞肺癌 (NSCLC) 细胞系中 PPARγ mRNA 和蛋白水平的影响尚未得到研究。因此,在我们的研究中,我们分析了c9,t11亚油酸异构体对两种不同组织学来源的NSCLC细胞系中PPARG和其他参与凋亡反应的基因(BCL-2、BAX和CDKN1A)表达的影响(A549 和 Calu-1)和正常人支气管上皮 Beas-2B 细胞。用数剂量的 c9,t11 CLA 处理细胞,然后进行 RNA 和蛋白质分离、cDNA 合成、实时定量 PCR (RT-qPCR) 和蛋白质印迹分析。我们表明,所研究的 CLA 异构体能够增强所检查细胞系中 PPARγ 的表达,并改变参与细胞凋亡的基因的 mRNA 和蛋白质水平。荧光染色和 MMT 测定揭示了 CLA 的抗增殖潜力及其激活导致细胞死亡的途径的能力。
更新日期:2020-01-30
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