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

doi:10.11958/20230797

Abstract

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

CLC Number:

R737.25

Figures/Tables 5

References 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.

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^＊

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^＊

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^＊＊

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^＊＊