Micellar curcumol for maintenance therapy of ovarian cancer by activating the FOXO3a

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-10-01 DOI:10.1016/j.nano.2024.102789
Jing Wang PhD, MD , Bing Chen MSc , Jiezhen Yang MSc , Qin Tang MSc , Yan Zhong MSc , Jiyu Du MSc , Sheng Wang MSc , Qiang Wu PhD, MD , Yang Lu PhD , Yonghong Song PhD
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Abstract

Maintenance therapy (MT) for ovarian cancer (OC) is crucial for preventing disease relapse. Curcumol shows effective anti-OC ability and low-toxicity to the normal ovarian epithelial cells, however, its bioavailability is low. Herein, micellar loaded curcumol (MC) was prepared and the anti-tumor ability of MC were performed on OC cells. The results indicated that the IC50 values of MC in two kinds of OC cells were 37.69 ± 2.43 and 28.54 ± 1.58 μg/mL, respectively. Mechanistically, curcumol could interact with the AKTThr308 site, inhibiting the phosphorylation of FOXO3a, which promoted FOXO3a nuclear locating and recruited it to the PERK promoter, activating the ERS induced apoptosis pathway. Moreover, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice and the DiR-labeled MC could quickly accumulate in the tumor region. MC provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products.

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通过激活 FOXO3a 使微胶囊姜黄醇用于卵巢癌的维持治疗。
卵巢癌(OC)的维持治疗(MT)对于防止疾病复发至关重要。姜黄醇具有有效的抗卵巢癌能力,且对正常卵巢上皮细胞毒性低,但其生物利用度较低。本文制备了胶束载体姜黄醇(MC),并对其在卵巢癌细胞上的抗肿瘤能力进行了研究。结果表明,MC 在两种 OC 细胞中的 IC50 值分别为 37.69 ± 2.43 和 28.54 ± 1.58 μg/mL。从机理上讲,姜黄醇可与AKTThr308位点相互作用,抑制FOXO3a的磷酸化,从而促进FOXO3a的核定位,并将其招募到PERK启动子上,激活ERS诱导的细胞凋亡途径。此外,MC还能抑制肿瘤裸鼠SKOV3细胞的生长,且DiR标记的MC能在肿瘤区域快速聚集。基于天然产物活性成分的纳米平台,MC为实现OC的高效MT提供了极大的可行性。
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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