龍葵堿對Panc-1細胞增殖和血管形成能力的影響及對AKT-mTOR通路的調節作用

楊嘹嘹，劉樂偉，謝建亮，陳旭鵬，黃智銘(.溫州醫科大學附屬樂清醫院消化科，浙江樂清35600；.溫州醫科大學附屬第一醫院消化科，浙江溫州35000)

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龍葵堿對Panc-1細胞增殖和血管形成能力的影響及對AKT-mTOR通路的調節作用

楊嘹嘹1，劉樂偉1，謝建亮1，陳旭鵬1，黃智銘2
(1.溫州醫科大學附屬樂清醫院消化科，浙江樂清325600；2.溫州醫科大學附屬第一醫院消化科，浙江溫州325000)

[摘 要]目的 探討龍葵堿對胰腺癌細胞Panc-1的增殖和血管形成能力的影響及其相關機制。方法 實驗分為對照組和藥物組，藥物組分別采用濃度為3.5、7.0和10.5 μmol/L的龍葵堿對細胞進行干預，軟瓊脂克隆試驗觀察龍葵堿對胰腺癌細胞Panc-1非貼壁依賴性增殖能力的影響；脈管形成實驗觀察龍葵堿對胰腺癌細胞Panc-1血管形成能力的影響；蛋白質免疫印跡(Western blotting)法檢測Panc-1細胞總蛋白中蛋白激酶B(protein kinase B，AKT)、雷帕霉素靶蛋白(target of rapamycin，mTOR)和血管內皮生長因子 (vascular endothelial growth factor，VEGF)的表達變化。結果 龍葵堿可明顯抑制Panc-1細胞非貼壁依賴性增殖能力，且呈劑量依賴性[100% vs (42.1±9.6)%，(24.3±8.5)%，(14.4±1.7)%；P＜0.05]；龍葵堿亦可抑制VEGF蛋白表達[100% vs (74.9±5.5)%，(31.9±6.8)%，(16.5±7.5)%，P＜0.05]，并且抑制脈管形成[100% vs (82.3±9.5)%，(76.9±8.9)%，(56.0±12.1)%，P＜0.05]；龍葵堿可下調Panc-1細胞AKT、mTOR磷酸化蛋白表達[100% vs (72.4±0.8)%，(59.4±1.3)%，(40.7±2.9)%；100% vs (96.7±0.4)%，(77.5±3.4)%，(34.1±7.6)%，P＜0.05]。結論 龍葵堿可能通過抑制AKT-mTOR細胞信號通路而抑制Panc-1細胞的增殖及血管形成能力。

[關鍵詞]龍葵堿；胰腺癌；增殖；血管形成；AKT-mTOR通路

Effects of Solanine on cell proliferation and angiogenesis of PANC-1 and its regulation on AKT-mTOR pathway YANG Liao-liao1, LIU Le-wei1, XIE Jian-liang1, CHEN Xu-peng1, HUANG Zhi-ming2.1Department of Gastroenterology Yueqing Hospital Af■liated to Wenzhou Medical University, Wenzhou, Zhejiang 325600, China;2Department of Gastroenterology, the First Af■liated Hospital of Wenzhou Medical University, Wenzhou 325000, China

Abstract ObjectiveTo investigate the effects of Solanine on proliferation and angiogenesis in pancreatic cancer cell line Panc-1 and explore its possible mechanisms.MethodsThe experiment was divided into two groups, Control group and Solanine group.In Solanine group the Panc-1 cells were treated with various concentrations of Solanine (3.5, 7.0 and 10.5 μmol/L).Cell proliferation and angiogenesis were detected with colony assay and tube formation assay.The protein expressions of VEGF (vascular endothelial growth factor), AKT (protein kinase B) -mTOR (target of rapamycin) were evaluated by Western blotting.ResultsSolanine inhibited proliferation of Panc-1 cells in a dose-dependent manner[100% vs (42.1±9.6)%, (24.3±8.5)%, (14.4±1.7)%；P＜0.05], as well as tube formation[100% vs (82.3±9.5)%, (76.9±8.9)%, (56.0±12.1)%； P＜0.05].The proein expression of VEGF was depressed by Solanine[100% vs (74.9±5.5)%, (31.9±6.8)%, (16.5±7.5)%； P＜0.05], decreased phosphorylation of AKT and mTOR were also found[100% vs (72.4±0.8)%, (59.4±1.3)%, (40.7±2.9)%；100% vs (96.7±0.4)%, (77.5±3.4)%, (34.1±7.6)%； P＜0.05].ConclusionThis study indicates that Solanine inhibits proliferation and angiogenesis via AKT-mTOR signaling pathways in Panc-1 cells.

Key words Solanine； pancreatic cancer； proliferation； angiogenesis； AKT-mTOR pathway

胰腺癌是一種惡性程度高、侵襲性強的癌癥，其五年生存率不足5%。由于早期診斷困難、藥物治療耐藥性高，預后不良，在世界癌癥死亡率中排名第4位[1]，在中國排名第6位[2]。手術治療是胰腺癌的主要手段，但存在術后并發癥重、生存期短的難題?！?br>