胃癌中ANP表达与BMP信号通路相互作用对细胞侵袭、转移的影响

目的探讨心房钠尿肽(atrial natriuretic peptide,ANP)在胃癌组织和细胞中的表达及ANP对胃癌细胞侵袭转移的作用。方法采用免疫组化EnVision法检测60例胃癌组织及正常胃黏膜组织中ANP的表达;培养胃癌细胞MGC-803,并将其分为两组:加入ANP组(ANP阳性组)、未加入ANP组(ANP阴性组)。采用Transwell实验检测两组胃癌细胞MGC-803的侵袭性,利用CCK8法检测两组胃癌细胞MGC-803的增殖能力。采用Western blot法检测两组胃癌细胞MGC-803中BMP信号通路相关蛋白表达量的变化及Ki-67、MMP-2和MMP-9蛋白表达量的变化。结果免疫组化检测ANP定位于胃黏膜细胞的胞质中,且在胃癌组织中的阳性率明显低于正常胃组织,差异有统计学意义(P<0.05);CCK8法、Transwell实验结果显示,ANP阳性组胃癌细胞的增殖速度及侵袭性比ANP阴性组低,差异有统计学意义(P均<0.05)。Western blot法检测ANP阳性组中BMP信号通路相关蛋白Smad1/5表达量比ANP阴性组低,差异有统计学意义(P<0.05);BMP6/7和p-Smad1/5的表达升高,差异有统计学意义(P均<0.05)。Western blot法检测ANP阳性组中Ki-67、MMP-2和MMP-9蛋白比ANP阴性组低,差异有统计学意义(P均<0.05)。结论胃癌组织中ANP的表达低于正常胃组织,ANP可能通过激活BMP信号通路抑制胃癌细胞MGC-803的增殖、侵袭和转移,为胃癌的发病机制及靶向治疗提供新思路。

Effect of interaction between the expression of atrial natriuretic peptide and BMP signaling pathway on cell invasion and metastasis in gastric cancer

Purpose To study the expression of atrial natriuretic peptide(ANP)in gastric canceRtissues and cells,and to explore its role in the invasion and metastasis of gastric canceRcells.Methods 60 cases of gastric canceRtissue and normal gastric mucosa tissue were collected.the expression of ANP was detected in these tissues by immunohistochemistry of EnVision.MGC-803 gastric canceRcells were cultured and divided into two groups:ANP(+)group with ANP and ANP(-)group without ANP.The invasiveness of MGC-803 gastric canceRcells in the two groups was detected by Transwell,and the proliferation ability of MGC-803 gastric canceRcells in the two groups was detected by CCK8.Western blot was used to detect the changes of BMP signaling pathway related proteins expression of the two groups,as well as the changes of Ki-67,MMP-2 and MMP-9 proteins expression.Results Immunohistochemistry result showed that ANP was located in the cytoplasm of gastric mucosal cell,and the positive expression rate in gastric canceRtissues was significantly loweRthan that in normal gastric tissues,with statistically significant difference(P<0.05).FurtheRanalysis showed that the proliferation rate and invasiveness of MGC-803 gastric canceRcells in the ANP(+)group were significantly loweRthan those in the ANP(-)group(all P<0.05).The expression of BMP signaling pathway related protein Smad1/5 in the ANP(+)group was significantly loweRthan that in the ANP(-)group by Western blot test(P<0.05).The expression of BMP6/7 and p-Smad1/5 increased,and the difference was statistically significant(all P<0.05).The expression of Ki-67,MMP-2 and MMP-9 proteins in the ANP(+)group was significantly reduced compared with the ANP(-)group in the control group by Western blot test,and the difference was statistically significant(all P<0.05).Conclusion ANP in gastric canceRtissues is loweRthan that in normal gastric tissues.ANP may inhibit the proliferation,invasion and metastasis of MGC-803 gastric canceRcells by activating the BMP pathway signaling pathway,which provides experimental basis foRthe pathogenesis of gastric canceRand new ideas of targeted therapy.