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四氧化三铁-苦马豆素诱导胰腺癌细胞凋亡并抑制其转移。

Fe3O4-solamargine induces apoptosis and inhibits metastasis of pancreatic cancer cells.

机构信息

Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210000, P.R. China.

Department of Intervention, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210000, P.R. China.

出版信息

Int J Oncol. 2019 Mar;54(3):905-915. doi: 10.3892/ijo.2018.4637. Epub 2018 Nov 19.

Abstract

Fe3O4-magnetic liposome (MLP) can deliver drugs to target tissues and can increase drug efficacy. The present study aimed to investigate the effects of solamargine (SM) and Fe3O4-SM in pancreatic cancer (PC). Cell viability was detected using a Cell Counting kit‑8 assay. Apoptosis and cell cycle progression was tested using a flow cytometry assay. A scratch assay was used to examine cell metastasis. Quantitative polymerase chain reaction, western blot analysis or immunohistochemical analysis were performed to determine the expression of target factors. Magnetic resonance imagining (MRI) and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling were conducted to detect tumor growth and apoptosis in vivo, respectively. It was demonstrated that Fe3O4-SM inhibited cancer cell growth via a slow release of SM over an extended period of time. SM was revealed to induce apoptosis and cell cycle arrest. Furthermore, SM decreased the expression of X-linked inhibitor of apoptosis, Survivin, Ki‑67, proliferating cell nuclear antigen and cyclin D1, but increased the activity of caspase-3. It was also observed that SM inhibited tumor cell metastasis by modulating the expression of matrix metalloproteinase (MMP)-2 and TIMP metallopeptidase inhibitor-2. Furthermore, the phosphorylation of protein kinase B and mechanistic target of rapamycin was suppressed by SM. Notably, the effect of SM was enhanced by Fe3O4-SM. The malignant growth of PC was decreased by SM in vivo. Furthermore, the expression of Ki‑67 was decreased by SM and Fe3O4-SM. Additionally, cell apoptosis was increased in the Fe3O4-SM group, compared with the SM group. The present study illustrated the antitumor effect and action mec-hanism produced by SM. Additionally, it was demonstrated that Fe3O4-SM was more effective than SM in protecting against PC.

摘要

四氧化三铁磁性脂质体 (MLP) 可以将药物递送到靶组织,并可以提高药物的疗效。本研究旨在探讨番茄红素 (SM) 和 Fe3O4-SM 在胰腺癌 (PC) 中的作用。使用细胞计数试剂盒 -8 检测细胞活力。通过流式细胞术检测细胞凋亡和细胞周期进程。划痕实验用于检测细胞转移。定量聚合酶链反应、western blot 分析或免疫组织化学分析用于确定靶因子的表达。磁共振成像 (MRI) 和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记用于检测体内肿瘤生长和细胞凋亡。结果表明,Fe3O4-SM 通过延长时间内 SM 的缓慢释放来抑制癌细胞生长。SM 诱导细胞凋亡和细胞周期停滞。此外,SM 降低了 X 连锁凋亡抑制剂、Survivin、Ki-67、增殖细胞核抗原和细胞周期蛋白 D1 的表达,但增加了 caspase-3 的活性。还观察到 SM 通过调节基质金属蛋白酶 (MMP)-2 和 TIMP 金属蛋白酶抑制剂-2 的表达来抑制肿瘤细胞转移。此外,SM 抑制了蛋白激酶 B 和雷帕霉素的作用机制靶点的磷酸化。值得注意的是,SM 的作用通过 Fe3O4-SM 得到增强。SM 在体内降低了 PC 的恶性生长。此外,SM 和 Fe3O4-SM 降低了 Ki-67 的表达。此外,与 SM 组相比,Fe3O4-SM 组细胞凋亡增加。本研究说明了 SM 产生的抗肿瘤作用和作用机制。此外,还证明了 Fe3O4-SM 在防治 PC 方面比 SM 更有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd8f/6365027/9541ea2086cb/IJO-54-03-0905-g00.jpg

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