ANGPT1影响小鼠前列腺癌细胞系RM-1增殖、侵袭及血管生成

doi:10.16352/j.issn.1001-6325.2025.09.1165

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (9): 1165-1172.doi: 10.16352/j.issn.1001-6325.2025.09.1165

ANGPT1影响小鼠前列腺癌细胞系RM-1增殖、侵袭及血管生成

安信, 贾麟, 马吾苏木·马木特, 黄志鹏, 卡哈尔曼·斯拉木, 热夏提·热合曼, 海日拉·吾拉木, 库尔班江·阿布力克木, 加素尔·巴吐尔^*

新疆喀什地区第一人民医院泌尿外科,新疆喀什 844000

收稿日期:2024-09-24 修回日期:2024-11-28 出版日期:2025-09-05 发布日期:2025-08-27
通讯作者: ^*Jesurbatur@163.com
基金资助:
省部共建中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2024-KY4);“天山英才”医药卫生高层次人才培养项目(TSYC202301B078);新疆维吾尔自治区自然科学基金(2021D01C017)

Effects of ANGPT1 on proliferation,invasion and angiogenesis of mouse prostate cancer cell line RM-1

AN Xin, JIA Lin, Mawusumu·MAMUT, HUANG Zhipeng, KahrimanI·SLAM, Rexiati·REHEMAN, Hairila·WULAMU, Kerbanjiang·ABULIKIM, Jesur·BATUR^*

Department of Urology, the First People′s Hospital of Kashgar, Kashgar 844000, China

Received:2024-09-24 Revised:2024-11-28 Online:2025-09-05 Published:2025-08-27
Contact: ^*Jesurbatur@163.com

摘要/Abstract

摘要： 目的解析血管生成素1(ANGPT1)对前列腺癌细胞增殖和侵袭及血管生成的调控机制。方法 1)将小鼠前列腺癌细胞系(RM-1)分为对照组、NC-oe组、ANGPT1-oe组、NC-sh组和ANGPT1-sh组。使用Lipofectamine 3000试剂将NC-oe、ANGPT1-oe、NC-sh和ANGPT1-sh转染至细胞RM-1。采用RT-qPCR和Western blot验证转染效率;MTT法和EdU染色检测细胞增殖;Transwell小室法检测细胞侵袭。2)细胞分组如下:对照组、Tie2的单核巨噬细胞(TEMs或TEM)组、NC-oe+TEM组、ANGPT1-oe+TEM组、NC-sh+TEM组和ANGPT1-sh+TEM组。按照分组情况,进行RM-1细胞与表达TEM共培养实验。培养72 h后,收集RM-1细胞并进行MTT实验、EdU染色实验和Transwell侵袭实验。收集共培养的各组细胞上清液,用于处理小鼠脐静脉内皮细胞(MUVECs),并检测小管形成数量。收集共培养的各组细胞上清液,采用ELISA检测MMP-9、VEGFA和COX-2水平。结果 1)与对照组和NC-oe组相比,ANGPT1-oe组细胞的ANGPT1 mRNA和蛋白相对水平升高(P＜0.05)。与对照组和NC-sh组相比,ANGPT1-sh组细胞的ANGPT1 mRNA和蛋白相对水平降低(P＜0.05)。2)与对照组相比,TEM组细胞的相对细胞活力、EdU阳性率、侵袭细胞数量和小管形成数量升高(P＜0.05),上清液中MMP-9、VEGFA和COX-2水平升高(P＜0.05)。与TEM组和NC-oe+TEM组相比,ANGPT1-oe+TEM组细胞的相对细胞活力、EdU阳性率、侵袭细胞数量和小管形成数量降低(P＜0.05),上清液中MMP-9、VEGFA和COX-2水平升高降低(P＜0.05)。与TEM组和NC-sh+TEM组相比,ANGPT1-sh+TEM组细胞的相对细胞活力、EdU阳性率、侵袭细胞数量和小管形成数量升高(P＜0.05),上清液中MMP-9、VEGFA和COX-2水平升高(P＜0.05)。结论前列腺癌中ANGPT1表达的降低进一步增强了TEMs对前列腺癌细胞系增殖、侵袭和血管生成的促进作用,从而促进了前列腺癌的进展。

关键词: 前列腺癌, 血管生成素1, 增殖, 侵袭, 血管生成

Abstract: Objective To explore the regulatory mechanism of angiopoietin 1 (ANGPT1) on proliferation, invasion and angiogenesis of prostate cancer cells. Methods Mouse prostate cancer cell line (RM-1) was divided into control group, NC-oe group, ANGPT1-oe group, NC-sh group and ANGPT1-sh group. NC-oe, ANGPT1-oe, NC-sh and ANGPT1-sh were transfected into RM-1 cells by Lipofectamine3000 reagent. The transfection efficiency was verified by RT-qPCR and Western blot, cell proliferation was detected by MTT assay and EdU staining and cell invasion was detected by Transwell assay. The cells were divided into the following groups: control group, Tie2-expressing monocytes/macrophages(TEMs) group, NC-oe+TEM group, ANGPT1-oe+TEM group, NC-sh+TEM group and ANGPT1-sh+TEM groups. RM-1 and TEM were co-cultured. RM-1 cells were collected after 72 hours and subjected to MTT proliferation assay, EdU staining assay and Transwell invasion assay. The co-cultured cell supernatant from each group mouse umbilical vein endothelial cells (MUVECs) were co-incubated with cell supernatant collected from each group cells and then to detect the number of tubules formed. The co-cultured cell supernatant of each group was collected, and the level of MMP-9, VEGFA and COX-2 were detected by ELISA. Results 1)Compared with control group and NC-oe group, the level of ANGPT1 mRNA and protein in ANGPT1-oe group was increased (P＜0.05). Compared with control group and NC-sh group, the level of ANGPT1 mRNA and protein in ANGPT1-sh group was decreased (P＜0.05). 2) Compared with control group, the cell viability, EdU positive rate, counting of invasive cells and of tubules formed in TEM group significantly increased(P＜0.05), the level of MMP-9, VEGFA and COX-2 in the supernatant was increased (P＜0.05). Compared with TEM group and NC-oe+TEM group, the cell viability, EdU positive rate, counting of invasive cells and of tubules formed in ANGPT1-oe+TEM group decreased (P＜0.05).The level of MMP-9, VEGFA and COX-2 in the supernatant was significantly decreased (P＜0.05). Compared with TEM group and NC-sh+TEM group, the cell viability, EdU positive rate, counting of invasive cell and of tubules formed in ANGPT1-sh+TEM group all increased (P＜0.05).The level of MMP-9, VEGFA and COX-2 in the supernatant were increased(P＜0.05). Conclusions The decreased expression of ANGPT1 in prostate cancer significantly enhances the promotion effect of TEMs on the proliferation, invasion and angiogenesis of prostate cancer cells, thus promoting the progression of prostate cancer.

Key words: prostate cancer, angiopoietin 1, proliferation, invasion, angiogenesis

中图分类号:

安信, 贾麟, 马吾苏木·马木特, 黄志鹏, 卡哈尔曼·斯拉木, 热夏提·热合曼, 海日拉·吾拉木, 库尔班江·阿布力克木, 加素尔·巴吐尔. ANGPT1影响小鼠前列腺癌细胞系RM-1增殖、侵袭及血管生成[J]. 基础医学与临床, 2025, 45(9): 1165-1172.

AN Xin, JIA Lin, Mawusumu·MAMUT, HUANG Zhipeng, KahrimanI·SLAM, Rexiati·REHEMAN, Hairila·WULAMU, Kerbanjiang·ABULIKIM, Jesur·BATUR. Effects of ANGPT1 on proliferation,invasion and angiogenesis of mouse prostate cancer cell line RM-1[J]. Basic & Clinical Medicine, 2025, 45(9): 1165-1172.

参考文献 15

[1]	方思尹, 刘辰, 吴晋晖. 微管抑制剂在血管新生性疾病中的作用机制研究进展[J]. 基础医学与临床, 2023, 43: 327-331.
[2]	Li Y, Liu P, Zhou Y, et al. Activation of angiopoietin-tie2 signaling protects the kidney from ischemic injury by modulation of endothelial-specific pathways[J]. J Am Soc Nephrol, 2023, 34: 969-987.
[3]	Anisimov A, Fang S, Hemanthakumar KA, et al. The angiopoietin receptor Tie2 is atheroprotective in arterial endothelium[J]. Nat Cardiovasc Res, 2023, 2: 307-321.
[4]	Wos＇ J, Chocholska S, Kowalska W, et al. Prognostic value of tie2-expressing monocytes in chronic lymphocytic leukemia patients[J]. Cancers (Basel), 2021, 13: 2817. doi:10.3390/cancers13112817.
[5]	Guo C, Buranych A, Sarkar D, et al. The role of tumor-associated macrophages in tumor vascularization[J]. Vasc Cell, 2013, 5: 20. doi:10.1186/2045-824X-5-20.
[6]	Nikas JB, Mitanis NT, Nikas EG. Whole exome and transcriptome RNA-sequencing model for the diagnosis of prostate cancer[J]. ACS Omega, 2020, 5: 481-486.
[7]	Yao S, Dong SS, Ding JM, et al. Sex-specific SNP-SNP interaction analyses within topologically associated domains reveals ANGPT1 as a novel tumor suppressor gene for lung cancer[J]. Genes Chromosomes Cancer, 2020, 59: 13-22.
[8]	Du Z, Zheng J, Zhang Z, et al. Review of the endothelial pathogenic mechanism of TIE2-related venous malformation[J]. J Vasc Surg Venous Lymphat Disord, 2017, 5: 740-748.
[9]	Fujiwara-Sumiyoshi S, Ueda Y, Fujikawa M, et al. Mucopolysaccharide polysulfate promotes microvascular stabilization and barrier integrity of dermal microvascular endothelial cells via activation of the angiopoietin-1/Tie2 pathway[J]. J Dermatol Sci, 2021, 103: 25-32.
[10]	Michael IP, Orebrand M, Lima M, et al. Angiopoietin-1 deficiency increases tumor metastasis in mice[J]. BMC Cancer, 2017, 17: 539. doi:10.1186/s12885-017-3531-y.
[11]	张成晶, 吴成亚, 冯颖, 等. 表达Tie2的单核巨噬细胞在肿瘤微环境形成中的作用及机制研究进展[J]. 肿瘤学杂志, 2018, 24: 904-909.
[12]	Elbanna M, Orillion AR, Damayanti NP, et al. Dual inhibition of angiopoietin-TIE2 and Met alters the tumor microenvironment and prolongs survival in a metastatic model of renal cell carcinoma[J]. Mol Cancer Ther, 2020, 19: 147-156.
[13]	Sopo M, Sallinen H, Hämäläinen K, et al. High expres-sion of Tie-2 predicts poor prognosis in primary high grade serous ovarian cancer[J]. PLoS One, 2020, 15: e0241484. doi:10.1371/journal.pone.0241484.
[14]	Yang WJ, Hao YX, Yang X, et al. Overexpression of Tie2 is associated with poor prognosis in patients with gastric cancer[J]. Oncol Lett, 2018, 15: 8027-8033.
[15]	Coffelt SB, Tal AO, Scholz A, et al. Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions[J]. Cancer Res, 2010, 70: 5270-5280.

ANGPT1影响小鼠前列腺癌细胞系RM-1增殖、侵袭及血管生成

Effects of ANGPT1 on proliferation,invasion and angiogenesis of mouse prostate cancer cell line RM-1

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 15

相关文章 15

编辑推荐

Metrics

本文评价

[1]	韦新闻, 温小军, 樊钊强, 劳锡峰, 张鲁青, 钟鸣. CircAPLP2通过调节miR-455-3p/STMN1轴抑制人结直肠癌细胞系增殖、迁移和侵袭[J]. 基础医学与临床, 2025, 45(9): 1208-1214.
[2]	邹庆波, 张国臣, 潘长景. 绞股蓝皂苷抑制人前列腺癌细胞系PC-3增殖、迁移和侵袭[J]. 基础医学与临床, 2025, 45(8): 1059-1065.
[3]	赵翠娟, 敖民, 武文博, 李妍华. 高脂饮食加重小鼠肠易激综合征肠屏障损伤[J]. 基础医学与临床, 2025, 45(8): 1022-1027.
[4]	田野, 何权, 王小娟. RPRD1B在人卵巢癌细胞系中高表达并促进肿瘤细胞增殖[J]. 基础医学与临床, 2025, 45(8): 1066-1072.
[5]	于华惠, 杜智勇, 焦晓璐, 吕倩雯, 杨云云, 韩丽杰, 秦彦文. 血管生成素样蛋白8通过激活p53信号通路促进平滑肌细胞凋亡[J]. 基础医学与临床, 2025, 45(7): 882-888.
[6]	殷利军, 卜阳, 昂格勒玛, 宋琳琳. LncRNA HIF1A-AS1通过干预HIF1A促进胃癌细胞系增殖[J]. 基础医学与临床, 2025, 45(5): 627-636.
[7]	魏建新, 房彦乐, 鲁雨博, 高宇光, 郎兴, 李静涛, 马新生. 青蒿琥酯抑制肾母细胞瘤细胞系SK-NEP-1增殖和促进凋亡与自噬[J]. 基础医学与临床, 2025, 45(4): 493-498.
[8]	周晶, 屈苗. 上调miR-152抑制ox-LDL诱导的人血管平滑肌细胞增殖和迁移[J]. 基础医学与临床, 2025, 45(4): 486-492.
[9]	张瑶, 张璇, 贾安娜, 战世佳, 郭金鑫, 常艳, 郭永丽. 嗅素结构域家族蛋白3促进MYCN扩增型神经母细胞瘤细胞系体外增殖[J]. 基础医学与临床, 2025, 45(2): 168-175.
[10]	姜华, 张贺, 江松松. 固醇调节元件结合蛋白1促进前列腺癌细胞增殖和侵袭[J]. 基础医学与临床, 2025, 45(2): 189-196.
[11]	杜红蕾, 张锋, 郭海彦, 徐宁, 吴震. 大车前苷抑制人胃癌细胞系BGC823增殖和侵袭[J]. 基础医学与临床, 2025, 45(10): 1333-1340.
[12]	张宗丽, 李涛, 马菁文, 张嘉鑫, 李兴朝, 席世兵. 氧浓度变化对人肺动脉内皮细胞中ANGPTL8表达的影响[J]. 基础医学与临床, 2025, 45(1): 12-19.
[13]	申红梅, 于燕, 冯绪强, 王克强. 松萝酸抑制人卵巢癌细胞系增殖[J]. 基础医学与临床, 2025, 45(1): 31-37.
[14]	张文倩, 周玥, 任卫东, 童安莉. 姜黄素对嗜铬细胞瘤细胞系PC12增殖及侵袭的影响[J]. 基础医学与临床, 2025, 45(1): 38-43.
[15]	肖艳红, 姜明东, 林叶远, 冉灿, 梁博. 灯盏花乙素抑制人前列腺癌细胞系PC-3的增殖和迁移[J]. 基础医学与临床, 2024, 44(9): 1229-1235.