Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway,Biomedicine & Pharmacotherapy

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Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2021-09-21 , DOI: 10.1016/j.biopha.2021.112174
Xinyue Tan ₁ , Liuyun Gong ₁ , Xinyue Li ₁ , Xinyue Zhang ₁ , Jiahao Sun ₁ , Xuehui Luo ₁ , Qi Wang ₁ , Jie Chen ₁ , Lina Xie ₁ , Suxia Han ₁

Affiliation

Aim

To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism.

Materials and methods

Targets of the drug promethazine (PMTZ) were identified by DrugBank and comparative toxicogenomic databases (CTD), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed with STRING software. The effects of PMTZ were predicted to be associated with the PI3K/AKT pathway. Cell Counting Kit 8 (CCK-8) assays were used to evaluate the effects of different concentrations of PMTZ on the proliferation of various types of CRC cells. Flow cytometry and Western blotting analyses were used to detect the degree of CRC cell apoptosis and the expression of the apoptosis-related proteins Bcl-2, Bax and caspase-3 after PMTZ treatment. The expression levels of PI3K/AKT pathway-related proteins [PI3K, AKT, phosphorylated (P)-PI3K and p-AKT] in CRC cells treated with PMTZ were analyzed by Western blotting.

Results

PMTZ inhibited the proliferation and promoted the apoptosis of CRC cells and suppressed the activation of the PI3K/AKT signaling pathway in a dose-dependent manner.

Discussion and conclusions

PMTZ may suppress the proliferation and induce the apoptosis of CRC cells by inhibiting the PI3K/ AKT signaling pathway. This study reported, for the first time, the function of PMTZ in CRC cells and the underlying mechanism and further confirmed the potential antitumor effects of phenothiazine. The combination of bioinformatics analyses and experiments provides informative evidence for the reuse of drugs and the development of new drugs.

中文翻译：

异丙嗪通过抑制 PI3K/AKT 通路抑制结直肠癌细胞增殖并促进细胞凋亡

目的

阐明异丙嗪对结直肠癌（CRC）细胞的潜在作用及其潜在机制。

材料和方法

通过DrugBank和比较毒物基因组数据库（CTD）确定药物异丙嗪（PMTZ）的靶点，并使用STRING软件进行京都基因和基因组百科全书（KEGG）通路分析。 PMTZ 的作用预计与 PI3K/AKT 通路相关。使用细胞计数试剂盒 8 (CCK-8) 检测评估不同浓度的 PMTZ 对各种类型 CRC 细胞增殖的影响。采用流式细胞术和Western blotting检测PMTZ处理后CRC细胞凋亡程度以及凋亡相关蛋白Bcl-2、Bax、caspase-3的表达量。通过蛋白质印迹法分析 PMTZ 处理的 CRC 细胞中 PI3K/AKT 通路相关蛋白 [PI3K、AKT、磷酸化 (P)-PI3K 和 p-AKT] 的表达水平。