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[1]陈莉洁,陈晨.西格列汀调节CCL2-CCR2 信号轴对前列腺癌细胞迁移、侵袭和免疫逃逸的影响[J].医学研究与战创伤救治(原医学研究生学报),2025,38(01):22-27.[doi:10.16571/j.cnki.2097-2768.2025.01.004]
　CHEN Lijie,CHEN Chen.Effects of sitagliptin on the migration，invasion，and immune escape of prostate cancer cells by regulatingthe CCL2-CCR2 signaling axis[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2025,38(01):22-27.[doi:10.16571/j.cnki.2097-2768.2025.01.004]
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西格列汀调节CCL2-CCR2 信号轴对前列腺癌细胞迁移、侵袭和免疫逃逸的影响()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
38卷
期数:
2025年01期
页码:
22-27
栏目:
论著·基础研究
出版日期:
2025-01-20

文章信息/Info

Title:
Effects of sitagliptin on the migration，invasion，and immune escape of prostate cancer cells by regulatingthe CCL2-CCR2 signaling axis
文章编号:
2097-2768（2025）01-0022-06
作者:
陈莉洁; 陈晨
作者单位：250000 济南，解放军联勤保障部队第九六〇医院第一派驻门诊部（陈莉洁、陈晨）
Author(s):
CHEN Lijie; CHEN Chen
（The First Outpatient Department of the 960th Hospital of the Joint Logistics Support Force，PLA，Jinan 250000，Shandong,China）
关键词:
西格列汀; CCL2-CCR2信号轴; 前列腺癌; 迁移、侵袭; 免疫逃逸
Keywords:
sitagliptin; CCL2-CCR2 signal axis; prostate cancer; migration and invasion; immune escape
分类号:
R737.25
DOI:
10.16571/j.cnki.2097-2768.2025.01.004
文献标志码:
A
摘要:
目的 探讨西格列汀（Sit）调节CC趋化因子配体2（CCL2）-CC趋化因子受体2（CCR2）信号轴对前列腺癌细胞迁移、侵袭和免疫逃逸的影响。方法将前列腺癌PC3细胞分为CK组、西格列汀低剂量（Sit-L）组、西格列汀高剂量（Sit-H）组、Sit-H+pcDNA-NC组、Sit-H+pcDNA-CCL2组。克隆形成实验检测细胞增殖；Transwell实验检测细胞迁移和侵袭；流式细胞术检测细胞凋亡率；酶联免疫吸附法（ELISA）检测细胞上清中趋化因子配体（CXCL-2、CXCL-8）水平；实时荧光定量聚合酶链反应（qRT-PCR）法检测细胞中CCL2 mRNA、CCR2 mRNA表达水平；蛋白免疫印迹法（Western blot）检测细胞增殖细胞核抗原（PCNA）、基质金属肽酶9（MMP-9）、半胱氨酸蛋白酶3（cleaved caspase-3）、CCL2、CCR2蛋白表达；将上述各组细胞与NK-92MI细胞共培养，细胞计数（CCK-8）法检测NK-92MI细胞免疫杀伤率；ELISA检测共培养细胞上清液中肿瘤坏死因子-α（TNF-α）、γ-干扰素（IFN-γ）水平。结果与CK组相比，Sit-L组、Sit-H组和Sit-H+pcDNA-NC组PC3细胞克隆形成率、细胞迁移和侵袭个数、CXCL-2、CXCL-8水平、CCR2 mRNA和CCL2 mRNA的表达水平、PCNA、MMP-9、CCL2、CCR2蛋白表达水平显著降低（P<0.05），细胞凋亡率、cleaved caspase-3蛋白表达水平显著升高（P<0.05）；过表达CCL2可减弱Sit对PC3细胞的抑制作用（P<0.05）；与CK-NK组共培养组比较，Sit-L-NK组、Sit-H-NK组和Sit-H+pcDNA-NC-NK组共培养组NK-92MI细胞免疫杀伤率、细胞上清中TNF-α、IFN-γ水平显著升高（P<0.05）；与Sit-H+pcDNA-NC-NK共培养组比较，Sit-H+pcDNA-CCL2-NK共培养组NK-92MI细胞免疫杀伤率，细胞上清中TNF-α、IFN-γ水平显著降低（P<0.05）。结论Sit通过抑制CCL2-CCR2信号轴可抑制前列腺癌细胞增殖、迁移、侵袭和免疫逃逸，并促进其凋亡。
Abstract:
Objective To investigate the effects of sitagliptin（Sit）on the migration，invasion and immune escape of prostatecancer cells by regulating the CC chemokine ligand 2（CCL2）- CC chemokine receptor 2（CCR2）signaling axis. Methods PC3cells were divided into CK group，sitagliptin low dose（Sit-L）group，Sitagliptin high dose（Sit-H）group，Sit-H+pcDNA-NC group andSit-H+pcDNA-CCL2 group. Cell proliferation was detected by clonal formation assay. Cell migration and invasion were detected byTranswell assay. The apoptosis rate was detected by flow cytometry. The chemokine ligands（CXCL-2，CXCL-8）in the supernatantwere detected by enzyme-linked immunosorbent assay（ELISA）. Re?al-time fluorescence quantitative polymerase chain reaction （qRTPCR）was used to detect the expression levels of CCL2 mRNA andCCR2 mRNA in cells. Western blot was used to detect the expressionof proliferating cell nuclear antigen（PCNA），matrix metallopeptidase9（MMP-9），cysteine protease 3（cleaved caspase-3），CCL2，andCCR2. The above groups of cells were co-cultured with NK-92MI cells，and CCK-8 method was used to detect the immune killing rate of NK-92MI cells. ELISA was applied to detect the levels of tumorbad factor-α（TNF-α）and γ-interferon（IFN-γ）in the supernatant of co-cultured cells. Results Compared with CK group，PC3cell clonal formation rate，number of cell migration and invasion，CXCL-2，CXCL-8 levels，CCR2 mRNA and CCL2 in Sit-L，Sit-H andSit-H+pcDNA-NC groups mRNA expression levels，protein expression levels of PCNA，MMP-9，CCL2，and CCR2 were significantly de?creased（P<0.05），and apoptosis rate and cleaved caspase-3 protein expression levels were significantly increased（P<0.05）. Overex?pression of CCL2 could weaken the inhibitory effect of Sit on PC3 cells（P<0.05）. Compared with the CK-NK group，the immune kill?ing rate of NK-92MI cells and the levels of TNF-α and IFN-γ in the cell supernatance of the Sit-L-NK group，SIT-H-NK group and Sit-H+pcDNA-NC-NK group were significantly increased（P<0.05）. Compared with the Sit-H+pcDNA-NC-NK co-culture group，the im?mune killing rate of NK-92MI cells and the levels of TNF-α and IFN-γ in the cell supernatant of the Sit-H+pcDNA-CCL2-NK co-cul?ture group were significantly decreased（P<0.05）. Conclusion Sit can inhibit the proliferation，migration，invasion and immune es?cape of prostate cancer cells and promote their apoptosis by inhibiting the CCL2-CCR2 signal axis.

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更新日期/Last Update: 2025-01-20