Hadisaputri Yuni Elsa, Nurhaniefah Annida Adha, Mutakin Mutakin, Hendriani Rini, Rezano Andri, Sopyan Iyan, Yusnaini Yusnaini, Asikin Yonathan, Abdulah Rizky
Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
J Exp Pharmacol. 2025 Jan 11;17:15-25. doi: 10.2147/JEP.S494158. eCollection 2025.
Lung cancer is recognized as a highly lethal disease, demanding swift and accurate solutions. Previous analysis showed the cytotoxic impact of extract containing ergost-22-en-3-one and ergost-7-en3-ol against A549 lung cancer cells, with an IC value of 9.38 μg/mL. However, the extract did not have cytotoxicity towards Het-1A esophagus epithelial cells. Several reviews also validated the upregulation of pro-apoptotic molecules and the inhibition of anti-apoptotic molecules linked to the caspase-dependent signaling pathway.
The objective of this research was to extend the understanding of the effects of extract on A549 lung carcinoma, examining its influence on various signaling pathways, malignancy, migration, and invasion.
PCR was used to measure expression, targeting , and . Additionally, Western Blot analysis was adopted to assess PTEN, p-Akt, Akt, p-mTOR, and p-STAT-3 protein expressions. Wound healing and invasion assays were performed to measure the migration and invasion capabilities of A549 cells post-treatment with extract.
The expression analysis showed an increase in and but a decrease in and after 24 hours of treatment with extract. At the protein level, there was a downregulation of p-Akt, Akt, p-mTOR, and p-STAT-3, while PTEN increased during 24-hour treatment. Wound healing and invasion assay results showed a weakened ability of A549 cells after a 24-hour treatment with extract. Moreover, and expression levels decreased during 24 hours, while mRNA had a slight decrease compared to untreated cells.
In conclusion, the ergosteroids present in marine sponge extract signified a remarkable reduction in malignancy, migration, and invasion capabilities in A549 lung carcinoma cells. These results suggested their promising candidacy for future anti-angiogenesis in anticancer therapy.
肺癌被认为是一种高度致命的疾病,需要迅速而准确的解决方案。先前的分析表明,含有麦角甾-22-烯-3-酮和麦角甾-7-烯-3-醇的提取物对A549肺癌细胞具有细胞毒性作用,IC值为9.38μg/mL。然而,该提取物对Het-1A食管上皮细胞没有细胞毒性。多项综述也证实了促凋亡分子的上调以及与半胱天冬酶依赖性信号通路相关的抗凋亡分子的抑制。
本研究的目的是进一步了解海绵提取物对A549肺癌的影响,研究其对各种信号通路、恶性程度、迁移和侵袭的影响。
采用PCR检测提取物处理后A549细胞中、和的表达。此外,采用蛋白质免疫印迹分析评估PTEN、p-Akt、Akt、p-mTOR和p-STAT-3蛋白的表达。进行伤口愈合和侵袭试验,以测量提取物处理后A549细胞的迁移和侵袭能力。
提取物处理24小时后,表达分析显示和增加,但和减少。在蛋白质水平上,p-Akt、Akt、p-mTOR和p-STAT-3下调,而PTEN在24小时处理期间增加。伤口愈合和侵袭试验结果显示,提取物处理24小时后A549细胞的能力减弱。此外,和的表达水平在24小时内下降,而与未处理细胞相比,mRNA略有下降。
总之,海绵提取物中的麦角甾类化合物显著降低了A549肺癌细胞的恶性程度、迁移和侵袭能力。这些结果表明它们在未来抗癌治疗的抗血管生成方面具有潜在的应用前景。