牡荆素通过线粒体途径和 PI3K/Akt/mTOR 信号通路诱导人非小细胞肺癌 A549 细胞凋亡。

Vitexin induces apoptosis through mitochondrial pathway and PI3K/Akt/mTOR signaling in human non-small cell lung cancer A549 cells.

机构信息

Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dongming Road, Zhengzhou City, 450008, Henan Province, People's Republic of China.

出版信息

Biol Res. 2019 Feb 23;52(1):7. doi: 10.1186/s40659-019-0214-y.

BACKGROUND

Currently, the prognosis of patients with non-small cell lung cancer (NSCLC) remains dismal; hence, it is critical to identify effective anti-NSCLC agents with limited side effects. This study aimed to evaluate the therapeutic potential of flavonoid compound vitexin in human NSCLC cells and the underlying mechanisms.

RESULTS

The experimental results indicated that vitexin reduced the viability of A549 cells in a dose-dependent manner with nearly no toxicity against normal human bronchial epithelial 16HBE cells. Vitexin also dose-dependently increased A549 cell apoptosis, accompanied by the decreased Bcl-2/Bax ratio and the increased expression of cleaved caspase-3. Moreover, the in vivo anticancer activity of vitexin was further determined in nude mice bearing A549 cells. In addition, vitexin induced the release of cytochrome c from the mitochondria to the cytosol and the loss of mitochondrial membrane potential. Vitexin also significantly reduced the levels of p-PI3K, p-Akt and p-mTOR, and the pro-apoptotic effect of vitexin on A549 cells was partly blocked by SC79, an Akt activator.

CONCLUSIONS

Accordingly, we believed that vitexin could be used as a potential therapeutic agent for the treatment of NSCLC in the future.

背景

目前，非小细胞肺癌（NSCLC）患者的预后仍然不佳；因此，识别具有有限副作用的有效抗 NSCLC 药物至关重要。本研究旨在评估类黄酮化合物牡荆素在人 NSCLC 细胞中的治疗潜力及其潜在机制。

结果

实验结果表明，牡荆素呈剂量依赖性降低 A549 细胞活力，对正常人支气管上皮 16HBE 细胞几乎没有毒性。牡荆素还呈剂量依赖性增加 A549 细胞凋亡，伴随着 Bcl-2/Bax 比值降低和 cleaved caspase-3 表达增加。此外，还在携带 A549 细胞的裸鼠中进一步确定了牡荆素的体内抗癌活性。此外，牡荆素诱导细胞色素 c 从线粒体向细胞质释放以及线粒体膜电位丧失。牡荆素还显著降低了 p-PI3K、p-Akt 和 p-mTOR 的水平，并且 Akt 激活剂 SC79 部分阻断了牡荆素对 A549 细胞的促凋亡作用。