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石蒜碱上调 RMB10 的表达,促进宫颈癌细胞凋亡,并抑制其增殖和迁移。

Lycorine upregulates the expression of RMB10, promotes apoptosis and inhibits the proliferation and migration of cervical cancer cells.

机构信息

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.

Vip Center, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.

出版信息

Int J Mol Med. 2022 Dec;50(6). doi: 10.3892/ijmm.2022.5201. Epub 2022 Nov 11.

DOI:10.3892/ijmm.2022.5201
PMID:36367172
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9662161/
Abstract

Although there are numerous treatment strategies, including surgery and chemotherapy, the prognosis of cervical cancer remains far from satisfactory. There is an urgent need to develop more effective, more tolerable and safer therapeutics for the treatment of cervical cancer. Lycorine is a natural plantextract that has been previously found to confer anti‑tumor activities. Therefore, in the present study, the effects of lycorine and its possible mechanism of action in cervical cancer were investigated. Cell Counting Kit‑8, wound healing and Transwell assays were used to verify the proliferation and migration of HeLa cells following lycorine intervention. The results demonstrated that lycorine significantly inhibited the proliferation and migration of HeLa cells. RNA binding motif 10 (RBM10) is a protein associated with apoptosis. It has been suggested that lycorine can affect the expression of RBM10. Flow cytometry demonstrated that lycorine may inhibit the initiation and progression of cervical cancer by promoting apoptosis, which may be mediated through the upregulation of RBM10 expression and increasing TNF‑α levels. Xenograft mouse experiments indicated that when lycorine was injected through the tail vein, HeLa tumor growth was inhibited. Mechanistically, western blotting demonstrated that lycorine significantly inhibited the activation of the Akt signaling pathway and potentially reversed epithelial‑mesenchymal transition, which was also mediated by RBM10. Furthermore, following RBM10 knockdown with small interfering‑RNA, the inhibitory effects of lycorine on cervical cancer was significantly abrogated. Overall, results of the present study suggest that lycorine can upregulate the expression of RBM10 and inhibit the proliferation and migration of cervical cancer cells.

摘要

虽然有许多治疗策略,包括手术和化疗,但宫颈癌的预后仍然远不理想。迫切需要开发更有效、更耐受和更安全的治疗方法来治疗宫颈癌。石蒜碱是一种天然植物提取物,先前已被发现具有抗肿瘤活性。因此,在本研究中,研究了石蒜碱及其在宫颈癌中可能的作用机制。细胞计数试剂盒-8、划痕愈合和 Transwell 测定用于验证石蒜碱干预后 HeLa 细胞的增殖和迁移。结果表明,石蒜碱显著抑制 HeLa 细胞的增殖和迁移。RNA 结合基序 10(RBM10)是一种与细胞凋亡相关的蛋白质。据报道,石蒜碱可以通过影响 RBM10 的表达来影响细胞凋亡。流式细胞术表明,石蒜碱可能通过促进细胞凋亡来抑制宫颈癌的发生和发展,这可能是通过上调 RBM10 的表达和增加 TNF-α水平来介导的。异种移植小鼠实验表明,当石蒜碱通过尾静脉注射时,HeLa 肿瘤生长受到抑制。从机制上讲,Western blot 表明石蒜碱显著抑制 Akt 信号通路的激活,并可能通过 RBM10 逆转上皮-间充质转化。此外,用小干扰 RNA 敲低 RBM10 后,石蒜碱对宫颈癌的抑制作用明显减弱。综上所述,本研究结果表明,石蒜碱可以上调 RBM10 的表达,抑制宫颈癌细胞的增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/70b8be90c9b4/IJMM-50-6-05201-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/65d11ec484ea/IJMM-50-6-05201-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/debacde960ee/IJMM-50-6-05201-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/4255ad04656b/IJMM-50-6-05201-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/3a3d12426e42/IJMM-50-6-05201-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/70b8be90c9b4/IJMM-50-6-05201-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/65d11ec484ea/IJMM-50-6-05201-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/debacde960ee/IJMM-50-6-05201-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/4255ad04656b/IJMM-50-6-05201-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/3a3d12426e42/IJMM-50-6-05201-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6b/9662161/70b8be90c9b4/IJMM-50-6-05201-g04.jpg

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