文章摘要
刘文杰,吴菡,黄建,等.人类表皮生长因子受体 2对胃癌细胞增殖、迁移侵袭和凋亡的影响[J].安徽医药,2021,25(2):299-303.
人类表皮生长因子受体 2对胃癌细胞增殖、迁移侵袭和凋亡的影响
Effects of HER2 on proliferation, migration, invasion and apoptosis of gastric cancer cells
  
DOI:10.3969/j.issn.1009-6469.2021.02.022.
中文关键词: 胃肿瘤  受体,表皮生长因子  增殖  迁移  侵袭  凋亡
英文关键词: Stomach neoplasms  Receptor, epidermal growth factor  Proliferation  Migration  Invasion  Apoptosis
基金项目:
作者单位
刘文杰 南京医科大学附属淮安第一医院病理科江苏淮安 223300 
吴菡 南京医科大学附属淮安第一医院病理科江苏淮安 223300 
黄建 南京医科大学附属淮安第一医院病理科江苏淮安 223300 
周武碧 南京医科大学附属淮安第一医院病理科江苏淮安 223300 
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中文摘要:
      目的研究人类表皮生长因子受体 2(HER2)对胃癌细胞增殖、迁移侵袭和凋亡的影响,并探讨其机制。方法 2018年 11月至 2019年 6月,运用实时定量 PCR(qRT-PCR)和蛋白质印迹法( Western blot)检测永生化的正常胃上皮细胞 GES-1、胃癌细胞 SGC-7901、MGC-803、BGC-823中 HER2的表达;将空载体( pcDNA 3.1)、 HER2过表达载体( pcDNA 3.1-HER2)、小干扰 RNA阴性对照( si-NC)、 HER2小干扰 RNA(si-HER2)用脂质体法转染至 SGC-7901细胞。噻唑蓝( MTT)法检测细胞增殖; Transwell小室检测细胞迁移和侵袭;流式细胞术检测细胞凋亡; Western blot检测细胞中 p16、p21、基质金属蛋白酶 9(MMP-9)、基质金属蛋白酶 2(MMP-2)、裂解的聚腺苷二磷酸核糖聚合酶( cleaved-PARP)、裂解的半胱氨酸蛋白酶 3(cleaved caspase-3)蛋白表达。结果与正常胃上皮细胞 GES-1相比,胃癌细胞 SGC-7901、MGC-803、BGC-823中 HER2的表达[( 3.02±0.28),(2.51±0.21)(2.36±0.19)比( 1.00±0.08)]明显升高,其中 SGC-7901细胞中的表达最高( P<0.05);过表达 HER2后, SGC-7901细胞的增殖[(1.1,2±0.09)比( 0.61±0.06)]、迁移[( 170±15)比( 100±9)]和侵袭[( 130±12)比( 75±6)]能力均明显上调,细胞的凋亡力[( 8.03±0.69)%比( 19.46±1.44)%]明显下调( P < 0.05);敲减 HER2则可下调 SGC-7901细胞的增殖[( 0.59±0.05)比( 0.89±0.08)]、迁移[( 55±5)比( 100±8)]和侵袭[( 36±4)比( 75±6)]能力,上调细胞的凋亡[( 16.82±1.15)%比( 8.01±0.65)%]能力( P<0.05)。重要的是,过表达 HER2可明显抑制 SGC-7901细胞中增殖抑制蛋白 p16、p21,迁移侵袭相关蛋白 MMP-2、MMP-9,凋亡促进相关蛋白 cleaved-PARP、cleaved caspase-3的表达,敲减 HER2具有相反的作用。结论 HER2可促进胃癌细胞的增殖、迁移侵袭,抑制凋亡,其可能与调控功能增殖、迁移侵袭及凋亡相关蛋白表达有关。
英文摘要:
      Objective To study the effect of Human epidermal growth factor receptor 2 (HER2) on the proliferation, migration, invasion and apoptosis of gastric cancer cells and to explore its mechanism.Methods From November 2018 to June 2019,Real-time quantitative PCR (qRT-PCR) and Western blot were used to detect the expression of HER2 in immortalized normal gastric epithelial cells GES-1, gastric cancer cells SGC-7901, MGC-803 and BGC-823. The empty vector (pcDNA 3.1), HER2 overexpression vector (pcDNA 3.1-HER2), small interfering RNA negative control (si-NC), and HER2 small interfering RNA (si-HER2) were transfected into SGC7901 cells by liposome method, respectively. Cell proliferation was detected by MTT assay, cell migration and invasion were detectedby Transwell chamber and cell apoptosis was detected by flow cytometry. Expressions of p16, p21, matrix metalloproteinase 9 (MMP-9), MMP-2, cleaved poly ADP ribose polymerase (cleaved-PARP), cleaved caspase-3 proteins were detected by Western blot. Results Compared with normal gastric epithelial cells GES-1, the expressions of HER2 in gastric cancer cells SGC-7901, MGC-803 and BGC823 [(3.02±0.28),(2.51±0.21),(2.36±0.19) vs. (1.00±0.08)] were significantly increased, and its expression in SGC-7901 cells was the highest (P < 0.05). After HER2 overexpression, the proliferation [(1.12±0.09) vs. (0.61±0.06)], migration [(170±15) vs. (100±9)] and invasion [(130±12) vs. (75±6)] of SGC-7901 cells were up-regulated, and the apoptotic ability [(8.03±0.69)% vs. (19.46±1.44)%] of cells was significantly down-regulated (P < 0.05). Knockdown of HER2 could down-regulate the proliferation [(0.59±0.05) vs. (0.89±0.08)], migration [(55±5) vs. (100±8)] and invasion [(36±4) vs. (75±6)] of SGC-7901 cells. The apoptotic ability [(16.82±1.15)% vs. (8.01± 0.65)%] of the cells was up-regulated (P < 0.05). Importantly, overexpression of HER2 significantly inhibited the expressions of proliferative inhibitory proteins p16, p21,migration-invasively related proteins MMP-2, MMP-9, cleaved-PARP and cleaved caspase-3 in SGC7901 cells. And Knockdown of HER2 had the opposite effect.Conclusion HER2 can promote the proliferation, migration and invasion of gastric cancer cells and inhibit apoptosis, which may be related to the regulation of functional proliferation, migration, invasionand apoptosis of related proteins.
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