Kauser Sana, Mughees Mohd, Mangangcha Irengbam Rocky, Swami Sanskriti, Wajid Saima
Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India.
Department of Zoology, Deshbandhu College, University of Delhi, Delhi, India.
Front Oncol. 2023 Aug 31;13:1209168. doi: 10.3389/fonc.2023.1209168. eCollection 2023.
(wormwood) exhibits anticancer properties by inhibiting proliferation and causing cell death in breast cancer. Targeted drug delivery of nanoformulation using N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid-based polymeric nanoparticles (NVA-AA NPs) was ensured by utilizing features of the tumor microenvironment, although their mechanism of action involved in cytotoxicity remains unknown.
The present study employed nano LC-MS/MS to identify differences in secretory protein expression associated with the treatment of breast cancer cell lines (MCF-7; MDA-MB-231) by NVA-AA NPs for the determination of affected pathways and easily accessible therapeutic targets. Different bioinformatics tools were used to identify signature differentially expressed proteins (DEPs) using survival analysis by GENT2 and correlation analysis between their mRNA expressions and sensitivity toward small-molecule drugs as well as immune cell infiltration by GSCA.
Analysis by GENT2 revealed 22 signature DEPs with the most significant change in their expression regulation, namely, gelsolin, alpha-fetoprotein, complement component C3, C7, histone H2B type 1-K, histone H2A.Z, H2AX, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1-like, cytochrome c somatic, GTP-binding nuclear protein Ran, tubulin beta chain, tubulin alpha-1B chain, tubulin alpha-1C chain, phosphoglycerate mutase 1, kininogen 1, carboxypeptidase N catalytic chain, fibulin-1, peroxiredoxins 4, lactate dehydrogenase C, SPARC, and SPARC-like protein 1. Correlation analysis between their mRNA expressions versus immune cell infiltrates showed a positive correlation with antitumor immune response elicited by these NPs as well as a correlation with drug response shown by the GDSC and CTRP drugs in different cancer cells.
Our results suggest that NVA-AA NPs were able to invade the tumor microenvironment; transformed the communication network between the cancer cells; affected potential drivers of microtubular integrity, nucleosome assembly, and cell cycle; and eventually caused cell death.
（艾草）通过抑制乳腺癌细胞增殖并导致细胞死亡展现出抗癌特性。利用肿瘤微环境的特征确保了使用N-异丙基丙烯酰胺、N-乙烯基吡咯烷酮和丙烯酸基聚合物纳米颗粒（NVA-AA NPs）进行纳米制剂的靶向药物递送，尽管其细胞毒性作用机制尚不清楚。
本研究采用纳米液相色谱-串联质谱法（nano LC-MS/MS）来识别与NVA-AA NPs处理乳腺癌细胞系（MCF-7；MDA-MB-231）相关的分泌蛋白表达差异，以确定受影响的途径和易于获取的治疗靶点。使用不同的生物信息学工具，通过GENT2进行生存分析以及通过GSCA分析它们的mRNA表达与对小分子药物的敏感性之间的相关性和免疫细胞浸润，来识别特征性差异表达蛋白（DEPs）。
GENT2分析揭示了22种特征性DEPs，其表达调控变化最为显著，即凝溶胶蛋白、甲胎蛋白、补体成分C3、C7、组蛋白H2B 1-K型、组蛋白H2A.Z、H2AX、热休克同源71 kDa蛋白、热休克70 kDa蛋白1样、细胞色素c体细胞、GTP结合核蛋白Ran、微管蛋白β链、微管蛋白α-1B链、微管蛋白α-1C链、磷酸甘油酸变位酶1、激肽原1、羧肽酶N催化链、纤连蛋白-1、过氧化物酶体增殖物激活受体4、乳酸脱氢酶C、富含半胱氨酸的酸性分泌蛋白（SPARC）和类SPARC蛋白1。它们的mRNA表达与免疫细胞浸润之间的相关性分析显示，与这些纳米颗粒引发的抗肿瘤免疫反应呈正相关，并且与不同癌细胞中GDSC和CTRP药物显示的药物反应相关。
我们的结果表明，NVA-AA NPs能够侵入肿瘤微环境；改变癌细胞之间的通讯网络；影响微管完整性、核小体组装和细胞周期的潜在驱动因素；并最终导致细胞死亡。
