CAJ | 학술논문

目的：研究肾上腺髓质素（ADM）对肾肿瘤细胞磷脂酰肌醇-3激酶（PI3K）／蛋白激酶B（Akt）／内皮型一氧化氮合酶（ eNOS）／血管内皮生长因子（ VEGF）信号通路的影响。方法将肾肿瘤细胞分为对照组、ADM组、VEGF组，ADM＋VEGF受体抑制剂组，ADM＋ADM shRNA组，每组设置24 h、48 h、72 h 3个时间梯度，western-blot检测对照组和ADM组细胞总蛋白中PI3K、Akt、eNOS、VEGF表达；检测VEGF组，ADM＋VEGF受体抑制剂组和ADM＋ADM shRNA组细胞总蛋白中PI3K、Akt、eNOS的表达。结果 PI3K、Akt、eNOS、VEGF在ADM组各时间梯度组肾肿瘤细胞中表达明显高于其在对照组细胞的表达（ P ＜0．05）。 PI3K、Akt、eNOS在VEGF组和ADM＋VEGF受体抑制剂组各时间组肾肿瘤细胞中表达明显高于其在对照组细胞中表达（ P ＜0．05）。 PI3K、Akt 、eNOS在ADM＋ADM shRNA组各时间组肾肿瘤细胞中表达与其在对照组细胞中表达差异无统计学意义（ P ＞0．05）。结论 ADM可激活PI3K／Akt／eNOS／VEGF信号通路；VEGF 受体抑制剂不能阻断 ADM 激活 PI3K／Akt／eNOS 信号通路。 ADM 一方面通过VEGF发挥肾肿瘤血管生成作用，另一方面通过其受体激活PI3K／Akt／eNOS信号通路参与肾肿瘤血管生成作用。ADM可能成为抗血管治疗肾肿瘤新的靶点。
목적：연구신상선수질소（ADM）대신종류세포린지선기순-3격매（PI3K）／단백격매B（Akt）／내피형일양화담합매（ eNOS）／혈관내피생장인자（ VEGF）신호통로적영향。방법장신종류세포분위대조조、ADM조、VEGF조，ADM＋VEGF수체억제제조，ADM＋ADM shRNA조，매조설치24 h、48 h、72 h 3개시간제도，western-blot검측대조조화ADM조세포총단백중PI3K、Akt、eNOS、VEGF표체；검측VEGF조，ADM＋VEGF수체억제제조화ADM＋ADM shRNA조세포총단백중PI3K、Akt、eNOS적표체。결과 PI3K、Akt、eNOS、VEGF재ADM조각시간제도조신종류세포중표체명현고우기재대조조세포적표체（ P ＜0．05）。 PI3K、Akt、eNOS재VEGF조화ADM＋VEGF수체억제제조각시간조신종류세포중표체명현고우기재대조조세포중표체（ P ＜0．05）。 PI3K、Akt 、eNOS재ADM＋ADM shRNA조각시간조신종류세포중표체여기재대조조세포중표체차이무통계학의의（ P ＞0．05）。결론 ADM가격활PI3K／Akt／eNOS／VEGF신호통로；VEGF 수체억제제불능조단 ADM 격활 PI3K／Akt／eNOS 신호통로。 ADM 일방면통과VEGF발휘신종류혈관생성작용，령일방면통과기수체격활PI3K／Akt／eNOS신호통로삼여신종류혈관생성작용。ADM가능성위항혈관치료신종류신적파점。
Obj ective To investigate the effect of the adrenomedullin on the signaling pathway of PI3K/Akt/eNOS/VEGF in renal tumor cell.M ethods The kidney tumor cells were divided into five groups,control group,ADM group,VEGF group, ADM +VEGF receptor inhibitor group, ADM +ADM shRNA group, moreover, every group was redivided three time gradient groups (24 hours,48 hours and 72 hours).The expression levels of PI3K,Akt,eNOS, VEGF in control group and ADM group and the expression levels of P3I K,Akt, eNOS in VEGF group,ADM+VEGF receptor inhibitor group,ADM +ADM shRNA group were detected by Western Blot,respectively.Results The expressions levels of the PI3K,Akt,eNOS,VEGF in ADM groups were significantly higher than those of control group ( P <0.05) .The expression levels of PI3K,Akt,eNOS in VEGF groups and ADM+VEGF receptor inhibitor groups were significantly higher than those of control group ( P <0.05). However there were no significant differences in the expression levels of PI3K, Akt, eNOS between ADM +ADM shRNA groups and control group ( P <0.05).C onclusion ADM can activate PI3K/Akt/eNOS signaling pathway in renal tumor cell,which can not be blocked by VEGF receptor inhibitor.On one hand ADM regulates renal tumor angiogenesis by VEGF,on the other hand,by activating PI 3K/Akt/eNOS signaling pathway to participate in renal tumor angiogenesis.ADM may become a promising anti-angiogenic target in the treatment of renal tumor.