Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Istanbul Sabahattin Zaim University, Istanbul, Turkey.
Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey.
Mol Biol Rep. 2022 Apr;49(4):2963-2971. doi: 10.1007/s11033-022-07117-6. Epub 2022 Jan 11.
Lung cancer (LC) is the most common types of cancer worldwide and is marked by high mortality rate. LC is classified into two major types due to their molecular and histological properties; non-small cell lung cancer (NSCLC) A549 and small cell lung cancer (SCLC). Currently, surgery, chemotherapy and radiation therapy are the most common treatment options of LC. However, the survival rate of LC is still very poor. Therefore, new treatment strategies are urgently needed. Erufosine (ErPC3) is a novel alkylphosphocholine and inhibits the translocation of Akt to the plasma membrane.
In the current study, the effects of ErPC3 in NSCLC cell line A549 and SCLC cell line DMS 114 in terms of cell viability, induction of apoptosis, cell cycle phase distribution, gene and protein expression levels, and migration capacity were investigated. 25 µM ErPC3 exhibited dose-dependent cytotoxicity against in both cancer cells. However, DMS 114 was more sensitive to ErPC3 than A549. Similarly, ErPC3 induced apoptotic cell ratio in DMS114 was significantly greater than A549. 25 µM ErPC3 caused the accumulation of both cell in G2/M phase. The levels of BCL-2 were downregulated and CASPASE 3-7 and BAX were upregulated while p-Akt levels were reduced in A549 and DMS 114 cells treated with 25 µM ErPC3. Besides, ErPC3 displayed anti-migratory effect on A549 and DMS 114.
These findings suggest that ErPC3 may be a promising novel therapeutic candidate for treatment of LC. ErPC3 treatment merits further investigation as potential agent against LC.
肺癌（LC）是全球最常见的癌症类型，其死亡率很高。LC 根据其分子和组织学特性分为两种主要类型；非小细胞肺癌（NSCLC）A549 和小细胞肺癌（SCLC）。目前，手术、化疗和放疗是 LC 的最常见治疗选择。然而，LC 的存活率仍然很差。因此，急需新的治疗策略。Erufosine（ErPC3）是一种新型的烷基膦胆碱，可抑制 Akt 向质膜的易位。
在本研究中，研究了 ErPC3 在 NSCLC 细胞系 A549 和 SCLC 细胞系 DMS 114 中的细胞活力、诱导细胞凋亡、细胞周期分布、基因和蛋白表达水平以及迁移能力方面的作用。25μM ErPC3 对两种癌细胞均表现出剂量依赖性细胞毒性。然而，DMS 114 对 ErPC3 的敏感性高于 A549。同样，ErPC3 诱导 DMS114 中凋亡细胞的比例明显大于 A549。25μM ErPC3 导致两种细胞均在 G2/M 期积累。BCL-2 水平下调，CASPASE 3-7 和 BAX 上调，而 p-Akt 水平在 A549 和 DMS 114 细胞中降低用 25μM ErPC3 处理。此外，ErPC3 对 A549 和 DMS 114 表现出抗迁移作用。
这些发现表明，ErPC3 可能是治疗 LC 的有前途的新型治疗候选物。ErPC3 治疗值得进一步研究，作为针对 LC 的潜在药物。
