PLR-3通过调控PI3K/Akt信号通路促进胃癌腹膜转移的研究

PLR-3 promotes peritoneal metastasis of gastric cancer by regulating PI3K/Akt signaling pathway

目的 探讨胃癌腹膜转移的发生机制,分析肝再生磷酸酶-3(PLR-3)是否通过调控PI3K/Akt信号通路影响胃癌腹膜转移,进而为疾病的治疗提供理论依据。方法 选取2015年6月—2021年12月间河南科技大学第一附属医院新区医院手术切除的胃癌组织标本216份,其中伴腹膜转移98份,无腹膜转移118份,Western blot检测其PLR3蛋白表达情况。选取胃癌SGC7901细胞系,通过PRL-3质粒转染构建PRL-3高表达细胞系和PRL-3低表达细胞系,通过划痕实验及Transwell小室测定两组细胞系的迁移及侵袭情况。Western blot检测两组细胞系中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶9(MMP-9)含量;采用RT-PCR检测两组细胞系中PI3K、Ak t mRNA变化,Western blot检测两组细胞系与上皮-间质转化(EMT)相关钙黏附蛋白E(E-cadherin)、N-钙蛋白(N-cadherin)及波形纤维蛋白(Vimentin)的表达情况。结果 腹膜转移胃癌组织中PLR3蛋白含量明显高于无腹膜转移胃癌组织(P<0.05);PRL-3高表达组细胞的迁移及侵袭能力明显高于低表达组(P<0.05);PRL-3高表达细胞中MMP-2、MMP-9含量明显高于低表达组(P<0.05);PRL-3高表达组细胞中PI3K、Ak t mRNA水平明显高于低表达组(P<0.05);E-cadherin相对表达量低于对照组,N-cadherin及Vimentin相对表达量表达高于对照组(P<0.05)。结论 腹膜转移是胃癌转移的常见类型之一,治疗困难,患者预后差,腹膜转移的发生机制较为复杂,尚未完全明确。PLR3激活PI3K/Akt信号能够促进胃癌腹膜转移,该通路可能是胃癌腹膜转移治疗的潜在靶点,对疾病的防治具有重要意义。

Objective To investigate the mechanism of peritoneal metastasis of gastric cancer and analyze whether liver regeneration phosphatase-3(PLR-3) affects peritoneal metastasis of gastric cancer by regulating PI3K/Akt signaling, so as to provide theoretical basis for the treatment of the disease. Methods Totally 216 gastric cancer tissue samples were selected from June 2015 to December 2021, including 98 with peritoneal metastasis and 118 without peritoneal metastasis. The expression of PLR-3 protein was detected by Western blot. Gastric cancer SGC7901 cell line was selected, and PRL-3 high expression cell line and PRL-3 low expression cell line were constructed by PRL-3 plasmid transfection. The migration and invasion of the two groups of cell lines were measured by scratch test and Transwell chamber. The contents of matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9(MMP-9) were detected by Western blot;The changes of PI3K and Akt in gastric cancer were detected by RT-PCR. Western blot was used to detect the expression of E-cadherin, N-cadherin and Vimentin related to epithelial mesenchymal transformation(EMT).Results The content of PLR-3 protein was significantly higher in gastric cancer tissues with peritoneal metastasis(P<0.05);The migration and invasion ability of PRL-3 high expression group was significantly higher than that of PRL-3 low expression group(P<0.05);The contents of MMP-2 and MMP-9 in PRL-3 high expression group were significantly higher than those in low expression group(P<0.05).The levels of PI3K and Akt mRNA in PRL-3 high expression group were significantly higher than those in low expression group(P<0.05). The relative expression of E-cadherin was lower than that of the control group, while the relative expression of N-cadherin and Vimentin was higher than that of the control group(P<0.05).Conclusion Peritoneal metastasis is one of the common types of gastric cancer metastasis. It is difficult to treat and the prognosis of patients is poor. The mechanism of peritoneal metastasis is complex and not completely clear.PRL-3 activation of PI3K/Akt signal can promote peritoneal metastasis of gastric cancer. This pathway may be a potential target for the treatment of peritoneal metastasis of gastric cancer, which is of great significance for the prevention and treatment of the disease.