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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
Received:27 February 2024,
Revised:2024-05-30,
Accepted:31 May 2024,
Published:15 July 2024
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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 [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 [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.
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。
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.
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