蜂毒液肽增强阿仑膦酸钠在 A549 肺癌细胞中的促凋亡活性。

Wasp venom peptide improves the proapoptotic activity of alendronate sodium in A549 lung cancer cells.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

PLoS One. 2022 Feb 24;17(2):e0264093. doi: 10.1371/journal.pone.0264093. eCollection 2022.

DOI:10.1371/journal.pone.0264093

PMID:35202419

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8872391/

Abstract

BACKGROUND

Lung cancer in men and women is considered the leading cause for cancer-related mortality worldwide. Anti-cancer peptides represent a potential untapped reservoir of effective cancer therapy.

METHODOLOGY

Box-Behnken response surface design was applied for formulating Alendronate sodium (ALS)-mastoparan peptide (MP) nanoconjugates using Design-Expert software. The optimization process aimed at minimizing the size of the prepared ALS-MP nanoconjugates. ALS-MP nanoconjugates' particle size, encapsulation efficiency and the release profile were determined. Cytotoxicity, cell cycle, annexin V staining and caspase 3 analyses on A549 cells were carried out for the optimized formula.

RESULTS

The results revealed that the optimized formula was of 134.91±5.1 nm particle size. The novel ALS-MP demonstrated the lowest IC50 (1.3 ± 0.34 μM) in comparison to ALS-Raw (37.6 ± 1.79 μM). Thus, the results indicated that when optimized ALS-MP nanoconjugate was used, the IC50 of ALS was also reduced by half. Cell cycle analysis demonstrated a significantly higher percentage of cells in the G2-M phase following the treatment with optimized ALS-MP nanoconjugates.

CONCLUSION

The optimized ALS-MP formula had significantly improved the parameters related to the cytotoxic activity towards A549 cells, compared to control, MP and ALS-Raw.

摘要

背景

肺癌在男性和女性中被认为是全球癌症相关死亡的主要原因。抗癌肽代表了一种潜在的、尚未开发的有效癌症治疗库。

方法

采用 Box-Behnken 响应面设计，应用 Design-Expert 软件对阿仑膦酸钠（ALS）- Mastoparan 肽（MP）纳米缀合物进行配方设计。优化过程旨在最小化制备的 ALS-MP 纳米缀合物的粒径。测定 ALS-MP 纳米缀合物的粒径、包封效率和释放曲线。对优化配方的 A549 细胞进行细胞毒性、细胞周期、Annexin V 染色和 caspase 3 分析。

结果

结果表明，优化配方的粒径为 134.91±5.1nm。与 ALS-Raw（37.6±1.79μM）相比，新型 ALS-MP 的 IC50（1.3±0.34μM）最低。因此，结果表明，当使用优化的 ALS-MP 纳米缀合物时，ALS 的 IC50 也降低了一半。细胞周期分析表明，用优化的 ALS-MP 纳米缀合物处理后，G2-M 期细胞的比例明显增加。