Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, 11787, Egypt.
Drug Microbiology Lab, Drug Radiation Research Department, National Center for Radiation Research and Technology, (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, 11787, Egypt.
BMC Complement Med Ther. 2023 May 20;23(1):162. doi: 10.1186/s12906-023-03986-x.
Breast cancer (BC) cells often develop multiple mechanisms of chemo- and radio-resistance during tumor progression, which is the major reason for the failure of breast cancer therapy. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Searching for chemo- and radio-sensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radio-sensitizer efficacy of amygdalin-folic acid nanoparticles (Amy-F) on MCF-7 and MDA-MB-231 cells.
The effects of Amy-F on MCF-7 and MDA-MB-231 cell proliferation and IC50 were assessed using MTT assay. The expression of proteins involved in several mechanisms induced by Amy-F in MCF-7 and MDA-MB-231 cells, including growth inhibition, apoptosis, tumor growth regulators, immuno-modulators, and radio-sensitizing activities were evaluated via flow cytometry and ELISA assay.
Nanoparticles demonstrated sustained Amy-F release properties and apparent selectivity towards BC cells. Cell-based assays revealed that Amy-F markedly suppresses cancer cell growth and improves radiotherapy (RT) through inducing cell cycle arrest (G1 and sub-G1), and increases apoptosis as well as reduces the proliferation of BC by down-regulating mitogen-activated protein kinases (MAPK/P38), iron level (Fe), nitric oxide (NO), and up-regulating the reactive oxygen species level (ROS). Amy-F has also been shown to suppress the expression of the cluster of differentiation (CD4 and CD80), and interfere with the Transforming growth factor beta (TGF- β)/Interferon-gamma (INF-g)/Interleukin-2 (IL-2)/Interleukin-6 (IL-6)/Vascular endothelial growth factor (VEGF) induced suppression in its signaling hub, while up-regulating natural killer group 2D receptor (NKG2D) and CD8 expression.
Collectively, the novel Amy-F either alone or in combination with RT abrogated BC proliferation.
乳腺癌（BC）细胞在肿瘤进展过程中常常会发展出多种化疗和放疗耐药机制，这是乳腺癌治疗失败的主要原因。与游离药物相比，靶向纳米药物在乳腺癌治疗中有巨大的治疗潜力。因此，迫切需要寻找化疗和放疗增敏剂来克服这种耐药性。本研究的目的是评估和比较苦杏仁苷-叶酸纳米粒（Amy-F）对 MCF-7 和 MDA-MB-231 细胞的放疗增敏作用。
采用 MTT 法检测 Amy-F 对 MCF-7 和 MDA-MB-231 细胞增殖及 IC50 的影响。采用流式细胞术和 ELISA 法检测 Amy-F 诱导 MCF-7 和 MDA-MB-231 细胞几种机制相关蛋白的表达，包括生长抑制、凋亡、肿瘤生长调节剂、免疫调节剂和放疗增敏活性。
纳米粒表现出持续释放 Amy-F 的特性，对乳腺癌细胞具有明显的选择性。细胞实验结果表明，Amy-F 能显著抑制肿瘤细胞生长，通过诱导细胞周期阻滞（G1 和 sub-G1），增加细胞凋亡，降低乳腺癌细胞增殖，改善放疗（RT）效果。此外，Amy-F 还能下调丝裂原激活蛋白激酶（MAPK/P38）、铁水平（Fe）、一氧化氮（NO），上调活性氧水平（ROS），下调分化簇（CD4 和 CD80）的表达，干扰转化生长因子-β（TGF-β）/干扰素-γ（INF-γ）/白细胞介素-2（IL-2）/白细胞介素-6（IL-6）/血管内皮生长因子（VEGF）信号通路，从而抑制其信号枢纽。同时，Amy-F 还能上调自然杀伤细胞组 2D 受体（NKG2D）和 CD8 的表达。
总之，新型 Amy-F 无论是单独使用还是与 RT 联合使用，均可抑制 BC 细胞增殖。
