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柳醇二甲醚通过激活细胞凋亡对喉癌细胞的制备及抑制作用。

Preparation and inhibitory effect of salicin dimethyl ether in Laryngeal cancer cells through the apoptosis activation.

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, China.

Department of Facial Features, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, China.

出版信息

Acta Biochim Pol. 2022 Oct 21;69(4):753-759. doi: 10.18388/abp.2020_5990.

DOI:10.18388/abp.2020_5990
PMID:36269869
Abstract

Laryngeal cancer is detected commonly worldwide, and it ranks second highest in incidence among the respiratory tract neoplasms following only head and neck squamous cell cancer. In the present study salicin dimethyl ether was synthesized and evaluated against laryngeal cancers cells for anticancer property. MTT assay was used for the measurement of changes in TU686 and Tu212 cell proliferation while as induced apoptosis was detected by flow cytometry. Protein expression was determined by western blotting and expression of mRNA by RT-PCR assay. In the present study salicin dimethyl ether was synthesized by the reaction of salicin with methyl iodide using sodium hydride as base. Salicin dimethyl ether treatment led to a significant decrease in TU686 and Tu212 cell proliferation in a dose-dependent manner. In TU686 and Tu212 cells salicin dimethyl ether treatment caused a significant increase in cell apoptosis and elevated caspase-3 activity. Treatment with salicin dimethyl ether led to a prominent reduction in Bcl-2 protein expression in TU686 and Tu212 cells at 72 h. Salicin dimethyl ether treatment led to a prominent decrease in p-PI3K and p-Akt protein expression in TU686 and Tu212 cells, compared to the untreated cells. A significant increase in miR‑15a expression in TU686 and Tu212 cells was observed on treatment with salicin dimethyl ether at 72 h. In summary, the current study demonstrates that salicin dimethyl ether, a synthetic derivative of salicin, suppresses proliferation of TU686 and Tu212 cells. The underlying mechanism involves induction of apoptosis, inhibition of PI3K/Akt pathway and promotion of miR-15a expression. Therefore, salicin dimethyl ether may be used for inhibition of laryngeal cancer growth, however, in vivo studies need to be conducted to confirm the effect.

摘要

喉癌是一种常见的全球性疾病,在呼吸道肿瘤中仅次于头颈部鳞状细胞癌,发病率位居第二。本研究合成了水杨苷二甲醚,并对其进行了抗癌活性评价。MTT 法用于检测 TU686 和 Tu212 细胞增殖变化,流式细胞术检测诱导的细胞凋亡。Western blot 检测蛋白表达,RT-PCR 检测 mRNA 表达。本研究通过水杨苷与碘甲烷在氢化钠作用下反应合成了水杨苷二甲醚。水杨苷二甲醚处理呈剂量依赖性显著降低 TU686 和 Tu212 细胞的增殖。在 TU686 和 Tu212 细胞中,水杨苷二甲醚处理显著增加细胞凋亡和升高 caspase-3 活性。水杨苷二甲醚处理 72 h 后,TU686 和 Tu212 细胞中 Bcl-2 蛋白表达明显减少。与未处理细胞相比,水杨苷二甲醚处理导致 TU686 和 Tu212 细胞中 p-PI3K 和 p-Akt 蛋白表达明显降低。水杨苷二甲醚处理 72 h 后,TU686 和 Tu212 细胞中 miR-15a 表达明显增加。综上所述,本研究表明,水杨苷的合成衍生物水杨苷二甲醚可抑制 TU686 和 Tu212 细胞的增殖。其作用机制可能涉及诱导细胞凋亡、抑制 PI3K/Akt 通路和促进 miR-15a 表达。因此,水杨苷二甲醚可能用于抑制喉癌的生长,但需要进行体内研究来证实其效果。

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