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CLMP通过抑制自噬增加结直肠癌对5-氟尿嘧啶的敏感性。

CLMP increases 5-fluorouracil sensitivity in colorectal cancer through the inhibition of autophagy.

作者信息

Yu Kun, Pu Hongjiang, Zhang Xuan, Yang Quan, Wang Weimin, Li Wenliang, Li Ziyu

机构信息

Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan Hospital, Yunnan Cancer Hospital, Kunming, Yunnan 650118, China.

Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan Hospital, Yunnan Cancer Hospital, Kunming, Yunnan 650118, China.

出版信息

Tissue Cell. 2025 Apr;93:102771. doi: 10.1016/j.tice.2025.102771. Epub 2025 Jan 30.

DOI:10.1016/j.tice.2025.102771
PMID:39922002
Abstract

BACKGROUND

We aimed to explore the biological function of CLMP in colorectal cancer (CRC) and to determine the effect of CLMP on 5-fluorouracil (5-FU) sensitivity in CRC.

METHODS

Sixteen pairs of CRC tissues and paracancerous tissues were collected. Immortalized intestinal epithelial cell lines and human CRC cell lines were purchased, and the cells were treated with DMSO and 5-FU. RTqPCR, western blotting, CCK8, colony formation, scratch, and Transwell assays were performed to determine the molecular mechanism of CLMP in the regulation of autophagy and sensitivity to 5-FU in CRC cells.

RESULTS

CLMP was expressed at low levels in CRC tissues. The upregulation of CLMP expression could inhibit cell proliferation, colony number, migration and invasion and increase the sensitivity of CRC cells to 5-FU. Mechanistic studies revealed that the overexpression of CLMP could block the activation of the PI3K/AKT signaling pathway, inhibit autophagy, and increase the chemosensitivity of CRC cells to 5-FU.

CONCLUSION

CLMP overexpression can reduce the level of autophagy and increase the sensitivity of CRC to 5-FU, providing a potential target for the treatment of CRC.

摘要

背景

我们旨在探究CLMP在结直肠癌(CRC)中的生物学功能,并确定CLMP对CRC中5-氟尿嘧啶(5-FU)敏感性的影响。

方法

收集16对CRC组织和癌旁组织。购买永生化肠上皮细胞系和人CRC细胞系,并用二甲基亚砜(DMSO)和5-FU处理细胞。进行逆转录定量聚合酶链反应(RTqPCR)、蛋白质免疫印迹法、细胞计数试剂盒-8(CCK8)、集落形成、划痕和Transwell实验,以确定CLMP在调控CRC细胞自噬及对5-FU敏感性中的分子机制。

结果

CLMP在CRC组织中低表达。CLMP表达上调可抑制细胞增殖、集落数量、迁移和侵袭,并增加CRC细胞对5-FU的敏感性。机制研究表明,CLMP过表达可阻断PI3K/AKT信号通路的激活,抑制自噬,并增加CRC细胞对5-FU的化学敏感性。

结论

CLMP过表达可降低自噬水平,增加CRC对5-FU的敏感性,为CRC治疗提供了一个潜在靶点。

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