川陈皮素调节EGFR/PI3K/AKT通路抑制前列腺癌细胞恶性生物学行为并促进凋亡  

Effect of Nobiletin on the Regulation of EGFR/PI3K/AKT Pathway to Inhibit Malignant Biological Behavior and Promote Apoptosis of Prostate Cancer Cells

作　　者：于湧[1] 乜国雁[1] 刘智明[1] 刘枫 靳锐 许玲芬[1] 谭光宏 YU Yong;NIE Guo-yan;LIU Zhi-ming;LIU Feng;JIN Rui;XU Ling-fen;TAN Guang-hong(Department of Urology,Qinghai Provincial People′s Hospital,Xining 810007,China)

机构地区：[1]青海省人民医院泌尿外科,青海西宁810007

出　　处：《中药材》2022年第11期2713-2718,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金项目(81860650)。

摘　　要：目的:探究川陈皮素对前列腺癌(PCa)细胞恶性生物学行为及凋亡的影响,并探讨其可能机制。方法:取对数期PC3细胞,随机分为对照组、川陈皮素(60μmol/L)组、表皮生长因子受体(EGFR)/磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)通路激活剂NSC228155(100μmol/L)组、联合组。MTT法检测细胞增殖能力;Annexin V/PI双染法检测细胞凋亡率;划痕实验检测细胞迁移能力;小室实验检测细胞侵袭能力;血管拟态实验检测细胞血管形成能力;免疫印迹法检测细胞EGFR、p-EGFR、AKT、p-AKT、mTOR、p-mTOR蛋白表达。结果:与对照组比较,川陈皮素组24、48、72 h光密度D(λ)值、迁移率、p-EGFR/EGFR、p-AKT/AKT、p-mTOR/mTOR显著降低,凋亡率显著升高,穿膜细胞数、血管支点数量显著减少(P<0.05);NSC228155组24、48、72 h光密度D(λ)值、迁移率、p-EGFR/EGFR、p-AKT/AKT、p-mTOR/mTOR显著升高,凋亡率显著降低,穿膜细胞数、血管支点数量显著增加(P<0.05)。与川陈皮素组比较,联合组24、48、72 h光密度D(λ)值、迁移率、p-EGFR/EGFR、p-AKT/AKT、p-mTOR/mTOR显著升高,凋亡率显著降低,穿膜细胞数、血管支点数量显著增加(P<0.05)。结论:川陈皮素可抑制PCa细胞增殖、迁移、侵袭及血管新生,并促进其凋亡,作用机制可能与抑制EGFR/PI3K/AKT信号通路有关。Objective:To investigate the effect of nobiletin on malignant biological behavior and apoptosis of prostate cancer(PCa) cells,to explore the possible mechanism.Methods:PC3 cells in logarithmic phase were randomly divided into control group,nobiletin(60 μmol/L) group,epidermal growth factor receptor(EGFR)/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT) pathway activator NSC228155(100 μmol/L) group,combination group.MTT assay was used to detect cell proliferation.Annexin V/PI double staining was used to detect the apoptosis rate.The migration ability of cells was detected by scratch test.Cell invasion ability was detected by chamber assay.Vascular mimicry test was used to detect angiogenesis ability of cells.The proteins expressions of EGFR,p-EGFR,AKT,p-AKT,mTOR and p-mTOR were detected by Western blotting.Results:Compared with the control group,the D(λ) value of optical density,mobility,p-EGFR/EGFR,p-AKT/AKT,p-mTOR/mTOR at 24,48 and 72 hours in nobiletin group were significantly decreased,apoptosis rate was significantly increased,the numbers of transmembrane cells and blood vessels were significantly decreased(P0.05).In NSC228155 group,the D(λ) value of optical density,mobility,p-EGFR/EGFR,p-AKT/AKT,p-mTOR/mTOR at 24,48 and 72 hours were significantly increased,apoptosis rate was significantly decreased,the numbers of transmembrane cells and blood vessels were significantly increased(P0.05).Compared with the nobiletin group,the D(λ) value of optical density,mobility,p-EGFR/EGFR,p-AKT/AKT,p-mTOR/mTOR at 24,48 and 72 hours in combined group were significantly increased,apoptosis rate was significantly decreased,the numbers of transmembrane cells and blood vessels/visual field were significantly increased(P0.05).Conclusion:Nobiletin can inhibit the proliferation,migration,invasion and angiogenesis of PCa cells,promote the apoptosis.The mechanism of action may be related to the inhibition of EGFR/PI3K/AKT signaling pathway.

关 键 词：川陈皮素 表皮生长因子受体 蛋白激酶B 前列腺癌 增殖 侵袭 凋亡 

分 类 号：R285.5[医药卫生—中药学]