Tra2-β1对缺氧子宫内膜癌细胞增殖、凋亡和转移的影响及其与临床病理特征的相关性

Effects of Tra2-beta1 on proliferation, apoptosis, and metastasis of hypoxic endometrial carcinoma cell and its correlation with clinicopathological features.

作者信息

Sun Wenhuizi, Paudel Dhruba, Song Sirui, Chen Kewei, Zhao Zhanqi, Chu Lei, Ouyang Yiqin

机构信息

Tongji University School of Medicine, Shanghai 200092, China.

Department of Obstetrics and Gynecology, Tongji Hospital of Tongji University, Shanghai 200065, China.

出版信息

Transl Cancer Res. 2020 Apr;9(4):2660-2671. doi: 10.21037/tcr.2020.02.66.

Abstract

BACKGROUND

This study aims to examine the influence of human transformer-2-beta1 (Tra2-beta1) on endometrial carcinoma (EC) development. The effects of Tra2-beta1 on the proliferation, apoptosis, invasion, and cell cycle of EC cells were also investigated.

METHODS

Functional experiments were performed on Tra2-beta1 knockdown cells and hypoxic model cells. Western blot was used to detect HIF-1a, vascular endothelial growth factor (VEGF), and Tra2-beta1 protein expression; CCK8 assay was used to detect cell proliferation; flow cytometry was used to detect apoptosis and cell cycle, and Transwell assay was used to detect cell invasion ability. Tumor specimens were collected from 128 consecutive patients to detect the expression of Tra2-beta1, and the relationship between and EC and Tra-beta1 were analyzed by clinical pathological data, which included lymph node metastasis, pathological types, histological grade, myometrial invasion, etc.

RESULTS

Tra2-beta1 was highly expressed in EC and was associated with clinical pathological features. It was related to the prognosis, and was found to promote proliferation (F=48.3, P<0.001) and migration (P<0.05), and inhibit apoptosis (P<0.05). Statistical analyses revealed a positive correlation between Tra2-beta1 and HIF-1a (correlation coefficient =0.36, P<0.001) and VEGF protein (correlation coefficient =0.23, P=0.021). In the hypoxic cell group and the combined intervention group, cell proliferation after 72 h was 9,783±45.6 and 6,783±68.4 (P<0.001), while the number of invasive cells was 421±16.8 and 276±11.2 (P<0.001), respectively. The apoptosis rates were 0.45±0.03 and 1.28±0.16, respectively (P<0.05).

CONCLUSIONS

The present findings demonstrate that the development of EC is positively correlated with Tra2-beta1. Tra2-beta1 may reverse the effect of hypoxia on EC, and this may provide new insights into the occurrence and development of EC.

摘要

背景

本研究旨在探讨人转化蛋白2-β1(Tra2-β1)对子宫内膜癌(EC)发生发展的影响。同时研究Tra2-β1对EC细胞增殖、凋亡、侵袭及细胞周期的作用。

方法

对Tra2-β1基因敲低细胞和缺氧模型细胞进行功能实验。采用蛋白质免疫印迹法检测缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)及Tra2-β1蛋白表达;采用细胞计数试剂盒8(CCK8)法检测细胞增殖;采用流式细胞术检测细胞凋亡及细胞周期;采用Transwell小室法检测细胞侵袭能力。收集128例连续患者的肿瘤标本检测Tra2-β1表达,并通过临床病理资料分析EC与Tra2-β1的关系,临床病理资料包括淋巴结转移、病理类型、组织学分级、肌层浸润等。

结果

Tra2-β1在EC中高表达,且与临床病理特征相关,与预后有关,可促进增殖(F=48.3,P<0.001)和迁移(P<0.05),抑制凋亡(P<0.05)。统计分析显示Tra2-β1与HIF-1α(相关系数=0.36,P<0.001)及VEGF蛋白(相关系数=0.23,P=0.021)呈正相关。在缺氧细胞组和联合干预组中,72小时后的细胞增殖数分别为9783±45.6和6783±68.4(P<0.001),而侵袭细胞数分别为421±16.8和276±11.2(P<0.001);凋亡率分别为0.45±0.03和1.28±0.16(P<0.05)。

结论

本研究结果表明EC的发生发展与Tra2-β1呈正相关。Tra2-β1可能逆转缺氧对EC的影响,这可能为EC的发生发展提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bc/8797671/8c95fc1abbbe/tcr-09-04-2660-f1.jpg

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