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

IF 3.6 3区 生物学 Q3 CELL BIOLOGY Journal of Cell Communication and Signaling Pub Date : 2024-12-19 DOI:10.1002/ccs3.12058
Nana Li, Peihua Yan, Ling Guo, Huiyan Wang, Baohong Cui, Lichen Teng, Yajuan Su
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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.

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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,找出卵巢癌化疗耐药的相关因素可能会逆转化疗敏感性。我们利用等压标签相对和绝对定量(ITRAQ)技术,找到了以附件蛋白1(ANXA1)为前体蛋白的小分子肽。随后,我们通过CCK-8、EdU细胞增殖实验、Annexin V-FITC/PI实验、Western blot、qRT-PCR等方法探讨了该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能促进卵巢癌细胞凋亡,提高卵巢癌细胞对顺铂的敏感性。ANXA114-26 和 ANXA1 可竞争性地结合甲酰肽受体(FPR)。ANXA114-26 通过 FPR/Cyclin D1/NF-ĸBp65 途径降低卵巢癌细胞中多药耐药性相关蛋白 1(MRP1)的表达。我们在卵巢癌患者的血清中发现了一种名为 ANXA114-26 的多肽。它能通过 FPR/Cyclin D1/NF-ĸBp65 途径减少卵巢癌细胞的增殖并降低 MRP1 的表达。
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来源期刊
CiteScore
6.40
自引率
4.90%
发文量
40
期刊介绍: The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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