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小分子肽ANXA114-26通过与甲酰肽受体结合来抑制卵巢癌细胞增殖并逆转顺铂耐药性。

The small molecule peptide ANXA114-26 inhibits ovarian cancer cell proliferation and reverses cisplatin resistance by binding to the formyl peptide receptors receptor.

作者信息

Li Nana, Yan Peihua, Guo Ling, Wang Huiyan, Cui Baohong, Teng Lichen, Su Yajuan

机构信息

Department of Clinical Laboratory Harbin Medical University Cancer Hospital Harbin China.

出版信息

J Cell Commun Signal. 2024 Dec 19;19(1):e12058. doi: 10.1002/ccs3.12058. eCollection 2025 Mar.

Abstract

Chemo-resistance in ovarian cancer is currently a major obstacle to the treatment and recovery of ovarian cancer. Therefore, identifying factors associated with chemo-resistance in ovarian cancer may reverse chemo-sensitization. Using isobaric tags for relative and absolute quantitation (ITRAQ) technology, we found a small molecule peptide with annexin 1 (ANXA1) as a precursor protein. Then, we explored the effects and mechanisms of this small molecule peptide on the proliferation, apoptosis, and drug resistance of ovarian cancer resistant cells through CCK-8, EdU cell proliferation assay, Annexin V-FITC/PI assay, Western blot,qRT-PCR. ANXA114-26 was highly expressed in the serums of sensitive patients. ANXA114-26 promoted apoptosis of ovarian cancer cells and increased the sensitization of ovarian cancer cells to cisplatin. The ANXA114-26 and ANXA1 competitively bind formyl peptide receptors (FPR). ANXA114-26 decreased multidrug resistance-associated protein 1 (MRP1) expression in ovarian cancer cells through the FPR/Cyclin D1/NF-ĸBp65 pathway. We found a peptide derived named ANXA114-26 in the serum of ovarian cancer patients. It can reduce ovarian cancer cell proliferation and reduce MRP1 expression through the FPR/Cyclin D1/NF-ĸBp65 pathway.

摘要

卵巢癌的化疗耐药性是目前卵巢癌治疗和康复的主要障碍。因此,识别与卵巢癌化疗耐药相关的因素可能会逆转化疗敏感性。利用相对和绝对定量同位素标记(ITRAQ)技术,我们发现了一种以前体蛋白膜联蛋白1(ANXA1)为基础的小分子肽。然后,我们通过CCK-8、EdU细胞增殖试验、膜联蛋白V-FITC/PI试验、蛋白质免疫印迹法、实时定量逆转录-聚合酶链反应,探讨了这种小分子肽对卵巢癌耐药细胞增殖、凋亡和耐药性的影响及机制。ANXA114-26在敏感患者血清中高表达。ANXA114-26促进卵巢癌细胞凋亡,并增加卵巢癌细胞对顺铂的敏感性。ANXA114-26与ANXA1竞争性结合甲酰肽受体(FPR)。ANXA114-26通过FPR/细胞周期蛋白D1/核因子-κB p65途径降低卵巢癌细胞中多药耐药相关蛋白1(MRP1)的表达。我们在卵巢癌患者血清中发现了一种名为ANXA114-26的衍生肽。它可以通过FPR/细胞周期蛋白D1/核因子-κB p65途径减少卵巢癌细胞增殖并降低MRP1表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6d/11659116/a0299b6605b8/CCS3-19-e12058-g005.jpg

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