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通过改变Bax/Bcl2的比例诱导肺癌细胞凋亡。

Induces Apoptosis in Lung Cancer Cells by Altering the Ratio of Bax/Bcl2.

作者信息

Yumrutas Onder, Yumrutas Pınar, Pehlivan Mustafa, Korkmaz Murat, Kahraman Demet

机构信息

Department of Medical Biology, Faculty of Medicine, Adıyaman University, 02200, Adıyaman, Turkey.

Department of Respiratory Disease and Cancer Biology, Faculty of Medicine, Gaziantep University, 27410, Gaziantep, Turkey.

出版信息

Anticancer Agents Med Chem. 2025;25(11):741-749. doi: 10.2174/0118715206333509241112060647.

DOI:10.2174/0118715206333509241112060647
PMID:39806957
Abstract

BACKGROUND

The lung cancer is the leading cause of death worldwide. Although methods such as surgery, chemotherapy, radiotherapy, and immunotherapy are used for treatment, these treatments are sometimes inadequate. In addition, the number of chemotherapeutic agents used is very limited, and it is very important to use new natural agents that can increase the effect of these methods used in treatment.

OBJECTIVE

The present study was designed to determine the suppression of proliferation and induction of apoptosis activities and phenolic content of methanol extract (OsME) on lung cancer cells (A549).

METHODS

For this purpose, the cell viability of A549 cells exposed to OsME was first determined. The morphological changes of the cell were observed by an inverted phase contrast microscope. Moreover, the percentage of apoptotic and necrotic cells was determined by FACS with AnnexinV/Propodium iodide staining. Additionally, proapoptotic Bax and antiapoptotic Bcl-2 mRNA levels were determined by Real-time PCR. Phenolic compounds of OsME were detected by LC-MS-MS.

RESULTS

It was observed that the viability and proliferation of lung cancer cells decreased after the treatment of different concentrations of OsME. At a concentration of 200 mg/ml of OsME, most of the cell membrane structures were observed to disintegrate. Meanwhile, a 25 μg/ml concentration of OsME increased the Bax expression and percentage of late apoptotic cells. Vanillic acid and luteolin were identified as the main phenolic compounds of OsME.

CONCLUSION

OsME exhibited antiproliferation activity on A549 cells and induced apoptosis at low doses.

摘要

背景

肺癌是全球主要的死亡原因。尽管采用了手术、化疗、放疗和免疫疗法等治疗方法,但这些治疗有时并不充分。此外,所用化疗药物的数量非常有限,因此使用能够增强治疗中所用这些方法效果的新型天然药物非常重要。

目的

本研究旨在确定甲醇提取物(OsME)对肺癌细胞(A549)的增殖抑制和凋亡诱导活性以及酚类含量。

方法

为此,首先测定了暴露于OsME的A549细胞的细胞活力。通过倒置相差显微镜观察细胞的形态变化。此外,采用膜联蛋白V/碘化丙啶染色,通过流式细胞术测定凋亡和坏死细胞的百分比。另外,通过实时聚合酶链反应测定促凋亡蛋白Bax和抗凋亡蛋白Bcl-2的mRNA水平。通过液相色谱-串联质谱法检测OsME中的酚类化合物。

结果

观察到不同浓度的OsME处理后,肺癌细胞的活力和增殖能力下降。在OsME浓度为200 mg/ml时,观察到大部分细胞膜结构解体。同时,25 μg/ml浓度的OsME增加了Bax的表达以及晚期凋亡细胞的百分比。香草酸和木犀草素被鉴定为OsME的主要酚类化合物。

结论

OsME对A549细胞具有抗增殖活性,并在低剂量时诱导凋亡。

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