染料木黄酮抑制前列腺癌进展和转移的机制研究

doi:10.11958/20230797

天津医药 ›› 2023, Vol. 51 ›› Issue (12): 1288-1292.doi: 10.11958/20230797

染料木黄酮抑制前列腺癌进展和转移的机制研究

刘文瞻¹(), 蔡启亮²^,^△(), 吴宝军³, 杨思维², 姚智力², 侯泽楷², 孙彬栩⁴

1.邯郸市第一医院泌尿一科（邮编056000）
2.天津医科大学第二医院泌尿外科
3.天津市津南医院泌尿外科
4.天津中医药大学附属第一医院肿瘤科

收稿日期:2023-05-27 修回日期:2023-10-14 出版日期:2023-12-15 发布日期:2023-12-22
通讯作者: ^△ E-mail：caiqiliang@tmu.edu.cn
作者简介:刘文瞻（1984），男，主治医师，主要从事泌尿系肿瘤的基础与临床研究。E-mail：zhan0624@126.com
基金资助:
天津市自然科学基金资助项目(21JCYBJC01470);天津市卫生健康委科技人才培育项目(KJ20137);天津市津南区科技计划项目(20161523)

Study on the mechanism of genistein inhibiting the progression and metastasis of prostate cancer

LIU Wenzhan¹(), CAI Qiliang²^,^△(), WU Baojun³, YANG Siwei², YAO Zhili², HOU Zekai², SUN Binxu⁴

1. Department I of Urology, Handan First People’s Hospital, Handan 056000, China
2. Department of Urology, the Second Hospital of Tianjin Medical University
3. Department of Urology, Jinnan Hospital of Tianjin
4. Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine

Received:2023-05-27 Revised:2023-10-14 Published:2023-12-15 Online:2023-12-22
Contact: ^△ E-mail：caiqiliang@tmu.edu.cn

刘文瞻, 蔡启亮, 吴宝军, 杨思维, 姚智力, 侯泽楷, 孙彬栩. 染料木黄酮抑制前列腺癌进展和转移的机制研究[J]. 天津医药, 2023, 51(12): 1288-1292.

LIU Wenzhan, CAI Qiliang, WU Baojun, YANG Siwei, YAO Zhili, HOU Zekai, SUN Binxu. Study on the mechanism of genistein inhibiting the progression and metastasis of prostate cancer[J]. Tianjin Medical Journal, 2023, 51(12): 1288-1292.

摘要/Abstract

摘要：

目的探讨染料木黄酮对前列腺癌细胞增殖、迁移和侵袭能力的影响及其分子机制。方法将前列腺癌细胞株LNCaP和CWR22RV1细胞分为对照组（常规培养）和实验组（50 μmol/L染料木黄酮处理）。采用噻唑蓝（MTT）法分析染料木黄酮对前列腺癌细胞增殖能力的影响，通过细胞划痕实验和Transwell实验分析染料木黄酮对前列腺癌细胞迁移及侵袭能力的影响。Western blot检测上皮间质转化（EMT）中间质标志物E-钙黏蛋白（E-Cadherin）、N-钙黏蛋白（N-Cadherin）、波形蛋白（Vimentin）以及肿瘤干细胞标志物CD44和Oct4的蛋白水平。结果 MTT实验结果表明，染料木黄酮具有抑制前列腺癌细胞增殖的作用。实验组LNCaP和CWR22RV1细胞划痕闭合率较对照组下调，穿过Transwell膜的细胞数量减少（P<0.05）。Western blot实验证实，染料木黄酮能够下调前列腺癌细胞中间质的标志物N-Cadherin、Vimentin和肿瘤干细胞的标志物CD44与Oct4蛋白表达，上调上皮细胞标志物E-Cadherin表达（P<0.01）。结论染料木黄酮通过抑制EMT过程并降低前列腺癌细胞的干性，从而降低前列腺癌细胞的增殖、迁移和侵袭能力。

关键词: 前列腺肿瘤, 染料木黄酮, 上皮-间质转化, 细胞运动

Abstract:

Objective To investigate the effect of genistein on the proliferation, migration and invasion of prostate cancer cells and its molecular mechanism. Methods Prostate cancer LNCaP and CWR22RV1 cells were divided into the control group (conventional culture) and the experimental group (50 μmol/L genistein treatment). The effect of genistein on the proliferation of prostate cancer cells were analyzed by MTT assay. The effect of genistein on the migration and invasion of prostate cancer cells were analyzed by cell scratch assay and Transwell assay. The protein levels of epithelial interstital transformation (EMT) intermediate markers E-Cadherin, N-Cadherin, Vimentin, and tumor stem cell markers CD44 and Oct-4 were detected by Western blot assay. Results MTT assay showed that genistein could inhibit the proliferation of prostate cancer cells. The scratch closure rates of LNCaP and CWR22RV1 cells were significantly reduced in the experimental group compared with those in the control group, and the number of cells passing through the Transwell membrane was significantly reduced (P<0.05). Western blot assay showed that genistein could down-regulate the expression levels of N-Cadherin, Vimentin, CD44 and Oct4 in prostate cancer cells, and up-regulate the expression of E-Cadherin in epithelial cells (P<0.01). Conclusion Genistein reduces the dryness of prostate cancer cells by inhibiting the EMT process, thus reducing the proliferation, migration and invasion of prostate cancer cells.

Key words: prostatic neoplasms, genistein, epithelial-mesenchymal transition, cell movement

中图分类号:

R737.25

图/表 5

表1 染料木黄酮对LNCaP和CWR22RV1细胞增殖活性的影响

Tab.1 Effect of genistein on proliferative activity of LNCaP and CWR22RV1 cells

组别	LNCaP细胞
组别	24 h		48 h		72 h
对照组	0.33±0.02		0.64±0.02		1.08±0.042
实验组	0.29±0.01		0.49±0.01		0.62±0.052
t	3.789^＊		11.340^＊＊		12.130^＊＊
组别		CWR22RV1细胞
组别		24 h		48 h		72 h
对照组		0.28±0.01		0.58±0.02		0.87±0.12
实验组		0.26±0.01		0.37±0.05		0.49±0.07
t		2.824^＊		6.970^＊		4.755^＊

图1 染料木黄酮对LNCaP 和CWR22RV1细胞的迁移的影响 A：LNCaP细胞；B：CWR22RV1细胞。

Fig.1 Effect of genistein on migration of LNCaP and CWR22RV1 cells

图2 染料木黄酮对LNCaP和CWR22RV1细胞侵袭的影响(结晶紫染色,×200)

Fig.2 Effect of genistein on invasion of LNCaP and CWR22RV1 cells (crystal violet staining, ×200)

图3 各组LNCap、CWR22RV1细胞中E-Cadherin, N-Cadherin, Vimentin, CD44、Oct-4的蛋白表达变化 A:实验组;B:对照组。

Fig.3 Changes of protein expression of E-Cadherin, N-Cadherin, Vimentin, CD44 and Oct-4 in LNCap and CWR22RV1 cells in each group

表2 各组LNCaP和CWR22RV1细胞E-Cadherin、N-Cadherin、Vimentin、CD44和Oct-4蛋白表达水平比较

Tab.2 Comparison of protein expressions of E-Cadherin, N-Cadherin, Vimentin, CD44 and Oct-4 in LNCaP and CWR22RV1 cells between the four groups（n=3，$\bar{x}±s$）

组别	LNCap细胞
组别	CD44	Oct-4	E-Cadherin	N-Cadherin	Vimentin
对照组	0.99±0.10	1.00±0.10	1.00±0.04	1.00±0.06	1.00±0.11
实验组	0.52±0.02	0.61±0.03	2.10±0.31	0.38±0.07	0.42±0.09
t	7.742^＊＊	6.173^＊＊	5.931^＊＊	10.595^＊＊	6.646^＊＊
组别	CWR22RV1细胞
组别	CD44	Oct-4	E-Cadherin	N-Cadherin	Vimentin
对照组	1.00±0.14	0.99±0.09	0.99±0.11	0.99±0.04	0.99±0.04
实验组	0.48±0.04	0.38±0.03	1.87±0.15	0.46±0.04	0.50±0.10
t	6.024^＊＊	10.879^＊＊	7.757^＊＊	14.541^＊＊	7.732^＊＊

参考文献 23

[1]	FITZMAURICE C, ABATE D, ABBASI N, et al. Global,regional,and national cancer incidence,mortality,years of life lost,years lived with disability,and disability-adjusted life-years for 29 Cancer Groups,1990 to 2017:a systematic analysis for the global burden of disease study[J]. JAMA Oncol, 2019, 5(12):1749-1768. doi:10.1001/jamaoncol.2019.2996.
[2]	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424. doi:10.3322/caac.21492.
[3]	CHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China,2015[J]. CA Cancer J Clin, 2016, 66(2):115-132. doi:10.3322/caac.21338.
[4]	刘瑾, 李文平. 前列腺癌耐药性与雄激素受体剪接变异体7关系的研究进展[J]. 中华实验外科杂志, 2019, 36(4):790-792.
	LIU J, LI W P. Advances in the relationship between prostate cancer resistance and androgen receptor splicing variant 7[J]. Chinese Journal of Experimental Surgery, 2019, 36(4):790-792. doi:10.3760/cma.j.issn.1001-9030.2019.04.064.
[5]	那彦群, 叶章群, 孙颖浩, 等. 中国泌尿外科疾病诊断治疗指南(2014版)[M]. 北京: 人民卫生出版社, 2013.
	NA Y Q, YE Z Q, SUN Y H, et al. Guidelines for the Diagnosis and Treatment of Urology Diseases in China (2014 Edition)[M]. Beijing: People's Health Publishing House, 2013.
[6]	叶定伟, 朱耀. 前列腺癌内分泌治疗的几个热点问题[J]. 临床外科杂志, 2006, 14(2):86-87.
	YE D W, ZHU Y. A few hot issues in endocrine therapy for prostate cancer[J]. Journal of Clinical Surgery, 2006, 14(2):86-87. doi:10.3969/j.issn.1005-6483.2006.02.014.
[7]	JI H F, LI X J, ZHANG H Y. Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia?[J]. EMBO Rep, 2009, 10(3):194-200. doi:10.1038/embor.2009.12.
[8]	WEI H, SALADI R, LU Y, et al. Isoflavone genistein:photoprotection and clinical implications in dermatology[J]. J Nutr, 2003, 133(<W>11 Suppl 1):3811S-3819 S. doi:10.1093/jn/133.11.3811S.
[9]	BANERJEE S, LI Y, WANG Z, et al. Multi-targeted therapy of cancer by genistein[J]. Cancer Lett, 2008, 269(2):226-242. doi:10.1016/j.canlet.2008.03.052.
[10]	LI Q S, LI C Y, LI Z L, et al. Genistein and its synthetic analogs as anticancer agents[J]. Anticancer Agents Med Chem, 2012, 12(3):271-281. doi:10.2174/187152012800228788.
[11]	徐丛荣, 魏建威, 曾敏玲, 等. 染料木黄酮对宫颈癌细胞增殖和侵袭的影响[J]. 医学理论与实践, 2017, 30(24):3617-3619.
	XU C R, WEI J W, ZENG M L, et al. Effects of genistein on proliferation and invasion of cervical cancer cells[J]. Medical Theory and Practice, 2017, 30(24):3617-3619. doi:10.19381/j.issn.1001-7585.2017.24.006.
[12]	ZHAO B, LIU L, MAO J, et al. Sinomenine hydrochloride attenuates the proliferation,migration,invasiveness,angiogenesis and epithelial-mesenchymal transition of clear-cell renal cell carcinoma cells via targeting Smad in vitro[J]. Biomed Pharmacother, 2017, 96:1036-1044. doi:10.1016/j.biopha.2017.11.123.
[13]	陈鹏, 邓小凡, 李波. 染料木黄酮对裸鼠肝癌切除术后肿瘤复发和转移的影响[J]. 中华肝脏病杂志, 2011, 19(2):140-141.
	CHEN P, DENG X F, LI B. Effects of genistein on tumor recurrence and metastasis after hepatectomy in nude mice[J]. Chinese Journal of Hepatology, 2011, 19(2):140-141. doi:10.3760/cma.j.issn.1007-3418.2011.02.020.
[14]	李飞, 朱彦锋, 陈静瑶, 等. 染料木黄酮对去势抵抗前列腺癌22RV1细胞增殖的影响[J]. 郑州大学学报(医学版), 2017, 52(4):393-398.
	LI F, ZHU Y F, CHEN J Y, et al. Effects of genistein on proliferation of castrate-resistant prostate cancer 22RV1 cells[J]. Journal of Zhengzhou University(Medical Sciences), 2017, 52(4):393-398. doi:10.13705/j.issn.1671-6825.2017.04.005.
[15]	李飞, 朱彦锋, 陈静瑶, 等. 染料木黄酮对去势抵抗性前列腺癌VCaP细胞增殖的影响[J]. 中华男科学杂志, 2016, 22(12):1065-1070.
	LI F, ZHU Y F, CHEN J Y, et al. Geinsten inhibits the proliferation of VCaP castration-resistant prostate cancer cells[J]. National Journal of Andrology, 2016, 22(12):1065-1070. doi:10.13263/j.cnki.nja.2016.12.002.
[16]	高晓康, 杨波, 王禾, 等. 染料木黄酮对前列腺癌细胞系PC-3生物学行为影响的意义[J]. 中国临床康复, 2004, 8(8):1580-1581.
	GAO X K, YANG B, WANG H, et al. Significance of genistein on PC-3 biological behavior of prostate cancer cell lines[J]. Clinical Rehabilitation in China, 2004, 8(8):1580-1581. doi:10.3321/j.issn:1673-8225.2004.08.060.
[17]	刘帅兵, 闫墨, 王楷斌, 等. GPR19基因在前列腺癌中的表达及意义[J]. 天津医药, 2022, 50(11):1128-1133.
	LIU S B, YAN M, WANG K B, et al. The expression and significance of GPR19 gene in prostate cancer[J]. Tianjin Med J, 2022, 50(11):1128-1133. doi:10.11958/20220419.
[18]	任智星, 杨光华. CDCA8通过调控增殖促进前列腺癌发生的作用机制研究[J]. 天津医药, 2022, 50(8):796-801.
	REN Z X, YANG G H. Study on the mechanism of CDCA8 promoting the occurrence of prostate cancer by regulating proliferation[J]. Tianjin Med J, 2022, 50(8):796-801. doi:10.11958/20212744.
[19]	曹玉霖, 李飞, 赵欢, 等. 染料木黄酮通过PI3K/AKT途径抑制雄激素非依赖性LNCaP细胞[J]. 安徽医科大学学报, 2018, 53(7):1017-1021.
	CAO Y L, LI F, ZHAO H, et al. Geinsten inhibits androgen independent LNCaP cells through the PI3K/AKT pathway[J]. Acta Universitatis Medicinalis Anhui, 2018, 53(7):1017-1021. doi:10.19405/j.cnki.issn1000-1492.2018.07.006.
[20]	TANG D G, PATRAWALA L, CALHOUN T, et al. Prostate cancer stem/progenitor cells: identification,characterization,and implications[J]. Mol Carcinog, 2007, 46(1):1-14. doi:10.1002/mc.20255.
[21]	SINGH A, SETTLEMAN J. EMT,cancer stem cells and drug resistance:an emerging axis of evil in the war on cancer[J]. Oncogene, 2010, 29(34):4741-4751. doi:10.1038/onc.2010.215.
[22]	SHANG Z, CAI Q, ZHANG M, et al. A switch from CD44⁺ cell to EMT cell drives the metastasis of prostate cancer[J]. Oncotarget, 2015, 6(2):1202-1216. doi:10.18632/oncotarget.2841.
[23]	ZHANG L, LI L, JIAO M, et al. Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway[J]. Cancer Lett, 2012, 323(1):48-57. doi:10.1016/j.canlet.2012.03.037.

染料木黄酮抑制前列腺癌进展和转移的机制研究

Study on the mechanism of genistein inhibiting the progression and metastasis of prostate cancer

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 5

参考文献 23

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张晋玮, 王燕, 王通. miR-107对口腔鳞癌细胞系CAL27增殖、侵袭及迁移的影响[J]. 天津医药, 2024, 52(9): 897-899.
[2]	马佳佳, 张亚苹, 杨斌, 赵美琪, 蒋璐, 黄小玉, 范路畅, 王凤梅. ATOX1通过JAK2/STAT3通路促进肝癌细胞生物学行为的机制探讨[J]. 天津医药, 2024, 52(9): 907-912.
[3]	张志华, 常泰浩, 罗飞, 王亚申, 李健. 同期前列腺穿刺联合PVP对高龄、高危、可疑前列腺癌患者的疗效及安全性[J]. 天津医药, 2024, 52(9): 959-962.
[4]	侯维玲, 乔云阳, 吴小芸, 施会敏, 曲高婷, 张爱青. 锌指蛋白281抑制高糖诱导的肾小管上皮细胞上皮间质转化和细胞外基质合成[J]. 天津医药, 2024, 52(7): 720-726.
[5]	刘丹阳, 李永涛, 张海燕, 李林, 刘洋, 沈雷. 乳腺癌细胞条件培养基对骨髓间充质干细胞生物学行为的影响[J]. 天津医药, 2024, 52(5): 454-458.
[6]	王鑫瑶, 杨惠, 李冰冰. 间充质干细胞在子宫内膜异位症中的研究进展[J]. 天津医药, 2024, 52(2): 215-219.
[7]	张贵婷, 何超. oxLDL/β2GPⅠ/aβ2GPⅠ复合物通过TLR4/MyD88/NF-κB途径促进血管内皮细胞血管生成[J]. 天津医药, 2024, 52(11): 1131-1136.
[8]	黄冠又, 葛学成, 甘鸿川, 郝淑煜, 吴震. CCL18在胶质母细胞瘤中的表达及其对U87MG细胞增殖和迁移的影响[J]. 天津医药, 2023, 51(9): 915-921.
[9]	岳巾晶, 曾莹, 郭晓珮, 董越, 姬若楠, 彭瑞, 罗晓华. miR-155通过调控PKG1影响滋养细胞生物学功能并参与子痫前期的机制探讨[J]. 天津医药, 2023, 51(9): 928-934.
[10]	王玉宁, 宋聚星, 田志刚, 郝国荣, 申浩. 白皮杉醇调控miR-106b-5p/RUNX3轴对宫颈癌细胞迁移及侵袭的影响[J]. 天津医药, 2023, 51(8): 814-819.
[11]	武海博, 梁燕, 沈雷, 范展, 傅国惠. 复方藤梨汤含药血清对人脑胶质瘤U251细胞增殖、凋亡及上皮间质转化的影响[J]. 天津医药, 2023, 51(8): 841-846.
[12]	黄昱刚, 谭伶娟, 陈广. 羽扇豆醇调控miR-100-5p对非小细胞肺癌NCI-H1299细胞生物学行为的影响[J]. 天津医药, 2023, 51(2): 118-123.
[13]	吴德建, 杨秋, 谢桂丹, 彭鑫. 紫草素调节Notch信号通路对肝癌细胞恶性生物学活性的影响[J]. 天津医药, 2023, 51(12): 1293-1299.
[14]	孙绪高, 杨文超, 刘彦杰, 杨旭. 茶黄素调节Snail/Slug信号通路对口腔鳞癌细胞生物学行为的影响[J]. 天津医药, 2023, 51(11): 1164-1169.
[15]	陈聪, 吴元肇, 郑克思, 应文兵, 胡逸人. 钙蛋白酶2通过诱导三阴乳腺癌细胞上皮间质转化抵抗紫杉醇的机制探讨[J]. 天津医药, 2023, 51(11): 1176-1180.