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DT-13 通过激活 AMPK-mTOR 信号通路诱导细胞凋亡抑制胰腺癌增殖。

DT-13 inhibits the proliferation of pancreatic cancer by inducing apoptosis via AMPK-mTOR signaling.

机构信息

Department of Breast, Thyroid and Vascular Surgery, Chongqing University FuLing Hospital, Chongqing, People's Republic of China.

Department of Clinical Laboratory, Chongqing University FuLing Hospital, Chongqing, People's Republic of China.

出版信息

Biochem Biophys Res Commun. 2024 Feb 5;695:149451. doi: 10.1016/j.bbrc.2023.149451. Epub 2023 Dec 30.

Abstract

BACKGROUND/OBJECTIVE: DT-13, the principal active component of Mysidium shortscapes from the Liliaceae family, has garnered substantial interest in cancer therapy owing to its potential anticancer properties. This study investigated the effects of DT-13 on the proliferation and apoptosis of human pancreatic cancer cell lines and aimed to elucidate the underlying mechanisms.

METHODS

PANC1 and CFPAC1 cells were exposed to DT-13 and their proliferation was assessed using RTCA and clone formation assays. Apoptotic protein expression was analyzed by western blotting, and apoptotic cells were identified by flow cytometry. RNA was extracted from DT-13 treated and untreated PANC1 cells for RNA sequencing. Differentially expressed genes were identified and subjected to GO bioprocess, KEGG pathway analysis, and western blotting. Finally, to evaluate tumor growth, CFPAC1 cells were subcutaneously injected into BALB/c nude mice.

RESULTS

DT-13 inhibited proliferation and induced apoptosis of PANC1 and CFPAC1 cells by activating the AMPK/mTOR pathway and suppressing p70 S6K. Moreover, DT-13 hindered the growth of CFPAC1 xenograft tumors in nude mice.

CONCLUSIONS

DT-13 effectively inhibited the growth of human pancreatic cancer cells.

摘要

背景/目的:来自百合科短叶贝母的主要活性成分 DT-13,由于其潜在的抗癌特性,在癌症治疗方面引起了广泛关注。本研究旨在探讨 DT-13 对人胰腺癌细胞系增殖和凋亡的影响,并阐明其潜在的机制。

方法

用 DT-13 处理 PANC1 和 CFPAC1 细胞,并用 RTCA 和克隆形成实验评估其增殖情况。通过 Western blot 分析凋亡蛋白的表达,并用流式细胞术鉴定凋亡细胞。提取 DT-13 处理和未处理的 PANC1 细胞的 RNA 进行 RNA 测序。鉴定差异表达基因,并进行 GO 生物过程、KEGG 通路分析和 Western blot。最后,为了评估肿瘤生长,将 CFPAC1 细胞皮下注射到 BALB/c 裸鼠中。

结果

DT-13 通过激活 AMPK/mTOR 通路和抑制 p70 S6K,抑制 PANC1 和 CFPAC1 细胞的增殖并诱导其凋亡。此外,DT-13 抑制了裸鼠中 CFPAC1 异种移植肿瘤的生长。

结论

DT-13 有效抑制了人胰腺癌细胞的生长。

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