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桃叶珊瑚苷对前列腺癌的抑制作用及机制的体内外研究
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| 篇名： | 桃叶珊瑚苷对前列腺癌的抑制作用及机制的体内外研究 |
| TITLE： | In vivo and in vitro study on the inhibitory effects and mechanism of aucubin on prostate cancer |
| 摘要： | 目的 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。方法将前列腺癌细胞PC3分为对照组、50μmol/LAU组、100μmol/LAU组、SC79（Akt激活剂）组（5μmol/L）、100μmol/LAU+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（80mg/kg）、SC79组（50mg/kg）和AU+SC79组（80mg/kgAU+50mg/kgSC79），每组10只，每天给药1次，共21d。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。结果细胞实验中，与对照组比较，50μmol/LAU组、100μmol/LAU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）；100μmol/LAU+SC79组与100μmol/LAU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 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 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 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 AU can inhibit PC cell proliferation and tumor growth by inhibiting Akt/MDM2/p53 signaling pathway. |
| 期刊： | 2024年第35卷第13期 |
| 作者： | 闫本纯；何春艳；李宏伟；南锡浩；张智慧；邸彦橙；田河 |
| AUTHORS： | YAN Benchun，HE Chunyan，LI Hongwei，NAN Xihao，ZHANG Zhihui，DI Yancheng，TIAN He |
| 关键字： | 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： | aucubin； Akt/MDM2/p53 signaling pathway； prostate cancer； proliferation； tumor growth |
| 阅读数： | 3 次 |
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