浏览全部资源
扫码关注微信
- Journal Information
- Archive
- Submission
- For Reviewers
- Statement and Policies
In vivo andin vitro study on the inhibitory effects and mechanism of aucubin on prostate cancer- ZHONGGUO YAOFANG Vol. 35, Issue 13, Pages: 1618-1623(2024)
- 作者机构：
1.牡丹江医学院附属红旗医院泌尿外科，黑龙江 牡丹江 157000
2.牡丹江医学院第一临床医学院，黑龙江 牡丹江 157011
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2024.13.13
CLC： R965Published：15 July 2024，
Received：27 February 2024，
Revised：30 May 2024，
- 稿件说明：
扫 描 看 全 文
闫本纯,何春艳,李宏伟等.桃叶珊瑚苷对前列腺癌的抑制作用及机制的体内外研究 Δ[J].中国药房,2024,35(13):1618-1623.
YAN Benchun,HE Chunyan,LI Hongwei,et al.In vivo and in vitro study on the inhibitory effects and mechanism of aucubin on prostate cancer[J].ZHONGGUO YAOFANG,2024,35(13):1618-1623.
闫本纯,何春艳,李宏伟等.桃叶珊瑚苷对前列腺癌的抑制作用及机制的体内外研究 Δ[J].中国药房,2024,35(13):1618-1623. DOI： 10.6039/j.issn.1001-0408.2024.13.13.
YAN Benchun,HE Chunyan,LI Hongwei,et al.In vivo and in vitro study on the inhibitory effects and mechanism of aucubin on prostate cancer[J].ZHONGGUO YAOFANG,2024,35(13):1618-1623. DOI： 10.6039/j.issn.1001-0408.2024.13.13.
摘要
目的
2
探讨桃叶珊瑚苷（AU）调节蛋白激酶B（Akt）/双微体同源基因2（MDM2）/p53信号通路对前列腺癌（PC）细胞增殖和肿瘤生长的影响。
方法
2
将前列腺癌细胞PC3分为对照组、50 μmol/L AU组、100 μmol/L AU组、SC79（Akt激活剂）组（5 μmol/L）、100 μmol/L AU+SC79组，考察各组细胞的克隆能力和增殖能力，检测细胞凋亡率及细胞中Akt/MDM2/p53信号通路相关蛋白表达。建立异种移植肿瘤裸鼠模型，并将建模成功的裸鼠分为肿瘤组、AU组（80 mg/kg）、SC79组（50 mg/kg）和AU+SC79组（80 mg/kg AU+50 mg/kg SC79 ），每组10只，每天给药1次，共21 d。末次给药后，称定肿瘤质量，检测肿瘤组织中细胞核相关抗原（Ki-67）及Akt/MDM2/p53信号通路相关蛋白表达。
结果
2
细胞实验中，与对照组比较，50 μmol/L AU组、100 μmol/L AU组细胞克隆形成数、增殖率和Akt、MDM2蛋白的磷酸化水平均显著减少/降低（
P
＜0.05），细胞凋亡率、p53蛋白表达水平均显著升高（
P
＜0.05），但SC79组各指标变化趋势相反（
P
＜0.05）；100 μmol/L AU+SC79组与100 μmol/L AU组比较，克隆形成数、增殖率和Akt、MDM2蛋白的磷酸化水平均显著增加/升高（
P
＜0.05），细胞凋亡率、p53蛋白表达水平均显著降低（
P
＜0.05），但与SC79组比较各指标变化趋势相反（
P
＜0.05）。体内实验中，与肿瘤组比较，AU组裸鼠的肿瘤质量及组织中Ki-67阳性表达和Akt、MDM2蛋白的磷酸化水平均显著降低（
P
＜0.05），p53蛋白表达水平显著升高（
P
＜0.05），但SC79组裸鼠的上述指标变化趋势相反（
P
＜0.05）；AU+SC79组与AU组比较，裸鼠的肿瘤质量及组织中Ki-67阳性表达和Akt、MDM2蛋白的磷酸化水平均显著升高（
P
＜0.05），p53蛋白表达水平显著降低（
P
＜0.05），但其与SC79组比较各指标变化趋势相反（
P
＜0.05）。
结论
2
AU可通过抑制Akt/MDM2/p53信号通路从而抑制PC细胞增殖及肿瘤生长。
Abstract
OBJECTIVE
2
To investigate the effects of aucubin （AU） on the proliferation and tumor growth of prostate cancer （PC） cells by regulating the protein kinase B （Akt）/murine double minute2 （MDM2）/p53 signaling pathway.
METHODS
2
Prostate cancer cell PC3 were separated into control group， 50 μmol/L AU group， 100 μmol/L AU group， SC79 （Akt activator） group （5 μmol/L）， and 100 μmol/L AU+SC79 group. The cell cloning and proliferation ability were investigated； the rate of cell apoptosis and the expressions of Akt/MDM2/p53 signaling pathway-related protein were detected. Meanwhile， xenograft tumor models of nude mice were constructed and separated into tumor group， AU group （80 mg/kg）， SC79 group （50 mg/kg）， and AU+SC79 group （80 mg/kg AU+50 mg/kg SC79）， with 10 mice in each group. They were given relevant medicine， once a day， for 21 d. After the last medication， tumor weight was determined， and the expressions of nucleus-associated antigen （Ki-67） and Akt/MDM2/p53 signaling pathway-related protein were detected in tumor tissue.
RESULTS
2
In the cell experiment， compared with control group， the cell clonal formation number， proliferation rate and phosphorylation levels of Akt and MDM2 protein in 50 μmol/L AU and 100 μmol/L AU groups were significantly decreased （
P
＜0.05）， while the cell apoptosis rate and p53 protein expression levels were significantly increased （
P
＜0.05）； however， the change trend of each index in SC79 group was opposite （
P
＜0.05）. Compared with 100 μmol/L AU group， the cell clonal formation number， proliferation rate and phosphorylation levels of Akt and MDM2 protein in 100 μmol/L AU+SC79 group were significantly increased （
P
＜0.05）， while cell apoptosis rate and p53 protein expression levels were significantly decreased （
P
＜0.05）； however， compared with SC79 group， the changing trend of indexes was the opposite （
P
＜0.05）. In the
in vivo
experiment， compared with the tumor group， the tumor mass and Ki-67 positive expression and the phosphorylation levels of Akt and MDM2 protein in nude mice of AU group were significantly decreased （
P
＜0.05）， and the expression level of p53 protein was significantly increased （
P
＜0.05）， but the changing trend of above indexes of nude mice
in SC79 group were opposite （
P
＜0.05）. Compared with AU group， the tumor mass， Ki-67 positive expression and phosphorylation levels of Akt and MDM2 protein in tumor tissues of nude mice in AU+SC79 group were significantly increased （
P
＜0.05）， while the expression level of p53 protein was significantly decreased （
P
＜0.05）； however， compared with SC79 group， the changing trend of above indexes was opposite （
P
＜0.05）.
CONCLUSIONS
2
AU can inhibit PC cell proliferation and tumor growth by inhibiting Akt/MDM2/p53 signaling pathway.
关键词
桃叶珊瑚苷Akt/MDM2/p53信号通路前列腺癌细胞增殖肿瘤生长
Keywords
Akt/MDM2/p53 signaling pathwayprostate cancerproliferationtumor growth
references
LEI Y H，CHAN M，LIU H Y，et al. Evodiamine as the active compound of evodiae fructus to inhibit proliferation and migration of prostate cancer through PI3K/Akt/NF-κB signaling pathway[J]. Dis Markers，2022，2022：4399334.
刘波，余佳，王坤，等. 烟管头草水提物对前列腺癌PC3细胞增殖、迁移与侵袭的影响[J]. 中国药房，2021，32（15）：1830-1836.
LIU B，YU J，WANG K，et al. Effects of water extract from Carpesium cernuum on proliferation，metastasis and invasion of prostate cancer PC3 cells[J]. China Pharm，2021，32（15）：1830-1836.
LIU L N，ZHANG Y，HU X，et al. MiR-138-5p inhibits prostate cancer cell proliferation and chemoresistance by targeting APOBEC3B[J]. Transl Oncol，2023，35：101723.
韩曼飞，张刘强，李医明. 天然桃叶珊瑚苷及其衍生物的化学结构和药理作用研究进展[J]. 中草药，2017，48（19）：4105-4113.
HAN M F，ZHANG L Q，LI Y M. Research progress on chemical structures and pharmacological effects of natural aucubin and its derivatives[J]. Chin Tradit Herb Drugs，2017，48（19）：4105-4113.
SHAO M，KUANG Z Y，WANG W L，et al. Aucubin exerts anticancer activity in breast cancer and regulates intestinal microbiota[J]. Evid Based Complement Alternat Med，2022，2022：4534411.
赵军军，鲁兰，卢欢，等. 车前草基于GEO芯片数据前列腺癌特征基因的生物信息学分析[J]. 江西中医药大学学报，2022，34（6）：70-74.
ZHAO J J，LU L，LU H，et al. Bioinformatics analysis of prostate cancer genes based on GEO databases of Planta- ginis Herba[J]. J Jiangxi Univ Chin Med，2022，34（6）：70-74.
SONG M Q，BODE A M，DONG Z G，et al. Akt as a therapeutic target for cancer[J]. Cancer Res，2019，79（6）：1019-1031.
GUPTA A，SHAH K，OZA M J，et al. Reactivation of p53 gene by MDM2 inhibitors：a novel therapy for cancer treat- ment[J]. Biomedecine Pharmacother，2019，109：484-492.
CHIBAYA L，KARIM B，ZHANG H，et al. MDM2 phosphorylation by Akt regulates the p53 response to oxidative stress to promote cell proliferation and tumorigenesis[J]. Proc Natl Acad Sci U S A，2021，118（4）：e2003193118.
HAN C T，SCHOENE N W，LEI K Y. Influence of zinc deficiency on Akt-MDM2-p53 and Akt-p21 signaling axes in normal and malignant human prostate cells[J]. Am J Physiol Cell Physiol，2009，297（5）：C1188-C1199.
冯淑炯，江巧丽. 桃叶珊瑚苷对人结肠癌HT-29细胞恶性生物学行为及SCAP/SREBP-1通路的影响[J]. 浙江中西医结合杂志，2021，31（6）：509-514.
FENG S J，JIANG Q L. Aucubin regulates malignant biological behavior of human colon cancer HT-29 cells possibly via SCAP/SREBP-1 pathway[J]. Zhejiang J Integr Tradit Chin West Med，2021，31（6）：509-514.
黄超，方兴刚，陈璐，等. 益母草碱调节Akt/MDM2/p53信号通路对脑胶质瘤细胞恶性生物学行为的影响[J]. 疑难病杂志，2023，22（10）：1090-1097.
HUANG C，FANG X G，CHEN L，et al. The effect of Leonurine regulation on the Akt/MDM2/p53 signaling pathway on the malignant biological behavior of glioma cells[J]. Chin J Difficult Complicat Cases，2023，22（10）：1090-1097.
CHENG J，SUN Y，ZHAO H C，et al. Niraparib restrains prostate cancer cell proliferation and metastasis and tumor growth in mice by regulating the lncRNA MEG3/miR-181-5p/GATA6 pathway[J]. PeerJ，2023，11：e16314.
夏红丽，田俊斌，李治琴. 桃叶珊瑚苷对膝骨关节炎小鼠的作用及机制实验研究[J]. 陕西医学杂志，2023，52（9）：1150-1154，1167.
XIA H L，TIAN J B，LI Z Q. Effects and mechanism of aucubin on knee osteoarthritis in mice[J]. Shaanxi Med J，2023，52（9）：1150-1154，1167.
陈姣蓉，洪小平，段妍君，等. 蛇床子素对特异性皮炎小鼠皮肤屏障及慢性瘙痒的作用[J]. 中成药，2021，43（12）：3489-3492.
CHEN J R，HONG X P，DUAN Y J，et al. Effects of osthole on skin barrier and chronic itching in mice with specific dermatitis[J]. Chin Tradit Pat Med，2021，43（12）：3489-3492.
ZHANG D，ZHAO K，HAN T，et al. Bisphenol A promote the cell proliferation and invasion ability of prostate cancer cells via regulating the androgen receptor[J]. Ecotoxicol Environ Saf，2024，269（1）：115818-115829.
CAO H W，FENG Y G，SUN P，et al. Zhoushi qiling decoction inhibits proliferation of human prostate cancer cells through IL-6/STAT3 pathway[J]. J Cancer，2023，14（12）：2246-2254.
LIAO Y H，CHEN F，TANG H S，et al. Extraction and purification of aucubin from Eucommia ulmoides seed draff in natural deep eutectic solvents using macroporous resins[J]. ACS Omega，2024，9（1）：1723-1737.
田莉，赵济华，徐晋珩，等. lncRNA OSTN-AS1下调miR-4461表达促进前列腺癌LNCaP细胞增殖、迁移和侵袭[J]. 医学分子生物学杂志，2023，9（3）：215-220.
TIAN L，ZHAO J H，XU J H，et al. LncRNA OSTN-AS1 promotes the proliferation，migration and invasion of pro- state cancer LNCaP cell by down-regulating miR-4461[J]. J Med Mol Biol，2023，9（3）：215-220.
HE S L，WANG W P，YANG Y S，et al. FAM3B promotes progression of oesophageal carcinoma via regulating the Akt-MDM2-p53 signaling axis and the epithelial-mesenchymal transition[J]. J Cell Mol Med，2019，23（2）：1375-1385.
0
Views
0
下载量
0
CSCD
- L-PDFDownload
- WORDDownload
- Meta-XMLDownload
- BibTeXDownload
- EndnoteDownload
- RefMan Download
- NoteExpressDownload
- NoteFirstDownload
Publicity Resources
Related Articles
Related Author
Related Institution
- Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
- Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号
公网安备50010302001817 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.