紫檀芪通过腺苷酸活化蛋白激酶抑制PC9细胞的机制  

Pterostilbene inhibits proliferation by regulating adenosine monophosphate - activated protein kinase signaling pathway in PC9 cells

作　　者：尚荣鑫[1] 刘金炜 王子乾 崔子期 张娇 朱以芳[1] 柯昌康[1] 蔡峰 韩国梁[1] Shang Rongxin;Liu Jinwei;Wang Ziqian;Cui Zigi;Zhang Jiao;Zhu Yifang;Ke Changkang;Cai Feng;Han Guoliang(Department of Thoracic Surgery, Tang Du Hospital, Fourth Military Medical University, Xi＇ an 710038, China;Department of Urology, the 62nd Central Hospi- tal of People＇s Liberation Army, Pu＇ er 665099, China;Company 7, Battalion 2, the First Bri- gade of Cadets, the Fourth Military Medical University, Xi＇ an 710032, China;Com- pany 1, Battalion 1, the First Brigade of Cadets, the Fourth Military Medical University, Xi＇ an 710032, Chin)

机构地区：[1]第四军医大学唐都医院胸外科,西安710038 [2]云南省普洱市解放军第62中心医院泌尿外科,665099 [3]第四军医大学一旅二营七连,西安710032 [4]第四军医大学一旅一营一连,西安710032

出　　处：《中华实验外科杂志》2018年第6期1091-1093,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察腺苷酸活化蛋白激酶（AMPK）通路对紫檀芪（PTE）诱导肺腺癌PC9细胞凋亡作用的影响。方法PTE组（15、30、60 μmol/L）处理后，检测细胞活性、凋亡率、线粒体膜电位（MMP）的变化；定量检测半胱氨酸天冬氨酸蛋白酶3（Caspase-3）活性，Western blot法检测AMPK通路和凋亡蛋白。此外，PTE联合AMPK特异性抑制剂（Com C）处理裸鼠荷瘤模型，观察瘤体增长速度及关键蛋白变化。结果PTE有效抑制PC9细胞活力[（56.15±7.22）%，P＝0.016]和MMP水平[（48.63±6.17）%，P＝0.013]，并增加细胞凋亡[（58.63±7.64）%，P＝0.033]和Caspase-3活性[（231.22±17.36）%，P＝0.018]，呈剂量依赖性；Western blot检测结果显示PTE上调AMPK（P＝0.036）和乙酰辅酶A羧化酶（ACC，P＝0.014）的磷酸化以及bcl-2相关X蛋白（bax，P＝0.042）的表达，抑制B淋巴细胞瘤-2基因编码蛋白（bcl-2，P＝0.010）的表达。此外，PTE有效抑制PC9裸鼠皮下瘤体增长速度，联合应用Com C则明显阻断上述抑制作用（P＝0.012）。结论PTE通过调控AMPK通路发挥抑制PC9细胞的作用，提示激活AMPK信号通路可能是治疗肺腺癌的新策略。Objective To investigate the effect of adenosine monophosphate-activated protein kinase （AMPK） signaling pathway on the process of apoptosis induced by pterostilbene （PTE） in human lung adenocarcinoma PC9 cells.MethodsThe PC9 cells were treated with PTE （0, 15, 30, and 60 μmol/L）. The cell of survival rate, apoptotic rate, and mitochondrial membrane potential （MMP） were respectively detected; the activity of Caspase-3 were probed; and Western blotting was used to detect the expressions of AMPK signaling and apoptosis related proteins, respectively. Moreover, Compound C （Com C）, a specific AMPK inhibitor, was applied to explore the regulation of apoptosis induced by PTE via AMPK pathway in vivo.Results After treated with PTE, PC9 cells displayed significant reductions in cell viability [（56.15±7.22）%, P=0.016] and MPP [（48.63±6.17）%, P=0.013], as well as increase of cell apoptosis [（58.63±7.64）%, P=0.033] and Caspase-3 [（231.22±17.36）%, P=0.018] in a dose-dependent manner. Western-bolt analysis showed that PTE treatments resulted in significant increases in phosphorylation of AMPK （P=0.036） and acetyl-CoA carboxylase （ACC, P=0.014）, and B cell lymphoma/leukemia-2 associated X protein （bax, P=0.042）, and a decrease of B cell lymphoma/leukemia-2 （bcl-2, P=0.010）. Results in vivo showed that PTE could inhibit the growth of PC9 cell xenografts. Furthermore, the combination of Com C significantly reversed the anti-cancer effect of PTE on PC9 cells （P=0.012）.Conclusion PTE is a potential inhibitor of PC9 cells by AMPK pathway in vitro and in vivo, which suggests that the activation of AMPK may be a novel therapeutic intervention for lung adenocarcinoma.

关 键 词：紫檀芪 肺腺癌 腺苷酸活化蛋白激酶 凋亡 PC9细胞 

分 类 号：R285.5[医药卫生—中药学]