PGAM1通过激活Warburg效应调控宫颈癌细胞恶性生物学行为的机制研究

Effect of PGAM1 on the biological behavior of cervical cancer cell by activating Warburg effect

目的探讨磷酸甘油酸变位酶1(PGAM1)在宫颈癌组织中的表达情况以及可能的生物学机制。方法收集行手术切除的67例宫颈癌患者的新鲜宫颈癌组织及癌旁正常组织,采用免疫组化法检测PGAM1的表达情况并分析与患者病理特征的关系。构建PGAM1基因沉默稳转Hela宫颈癌细胞株,分析PGAM1基因沉默对Hela细胞凋亡和增殖活性的影响。采用qRT-PCR和Western blot法检测PGAM1对Akt/m TOR信号通路关键分子的影响。结果 (1)宫颈癌组织中PGAM1高表达率为58.21%,明显高于癌旁组织(P<0.05)。(2)不同临床分期、分化程度、浸润深度的患者宫颈癌组织中PGAM1的高表达率差异有统计学意义(P<0.05)。(3)Hela细胞sh PGAM1基因沉默后,细胞凋亡率较空白对照组(NC组)明显增加,细胞增殖活性明显降低(P<0.05)。(4)Hela细胞sh PGAM1基因沉默后,与NC组比较,PTEN mRNA和蛋白相对表达量明显上调,而p-Akt、p-m TOR mRNA和蛋白相对表达量明显降低(P<0.05)。结论肿瘤组织PGAM1蛋白高表达与宫颈癌的发生、发展有关,通过激活Akt/m TOR信号通路诱导的Warburg效应,促使肿瘤细胞的增殖,抑制其凋亡。

Objective To investigate the expressions of phosphoglycerate mutase1（ PGAM1） in different types of human cervical cancer tissues,and to explore the related mechanisms involved. Methods 67 pairs of tumor and adjacent tissue samples from 67 patients with cervical cancer were collected. The expressions of PGAM1 in different types of human cervical tissues were detected by immunohistochemical staining. The shRNA expression vector targeting human PGAM1 gene was constructed and transfected into human cervical cancer cell line Hela. The effect of PGAM1 on proliferation and apoptosis of Hela cell was detected by MTT and FCM. And the effect of PGAM1 on expressions of Akt/m TOR signaling pathway was detected by qRT-PCR and Western blot. Results（1） The high expression rate of PGAM1 in cancer tissues was 58. 21%,which was higher than that of adjacent tissues（ P〈0. 05）.（2） There was statistical significance of the high expression rate of PGAM1 in cancer tissues with different clinical stages,differentiation degrees and invasion depth（ P〈0. 05）.（3） The apoptosis rate of Hela cells with PGAM1-specific shRNA which had more lower proliferation rate was higher than that of negative control（ NC） group（ P〈0. 05）.（4） The expression of PTEN mRNA and protein in Hela cells with sh PGAM1 was higher than that of NC group（ P〈0. 05）,whereas the expression of p-Akt and p-m TOR in sh PGAM1 Hela cells was lower than that of NC group（ P〈0. 05）. Conclusion There are significant evidences that PGAM1 up-regulation would be related with esophageal cancer,which promote the proliferation of Hela cells by activating the Akt/m TOR signaling pathway and Warburg effect.