摘要
目的:探究RAS相关的C3肉毒素底物1(RAC1)在胃癌中的表达及其与临床病理学特征的相关性,并观察RAC1对胃癌细胞的增殖、迁移等生物学特性的影响。方法:使用免疫组织化学染色方法研究RAC1在胃癌中的表达情况。分别使用χ2检验及Kaplan-Meier生存分析的统计学方法分析RAC1的表达与胃癌临床病理学的特征及预后的相关性。并探究高表达RAC1在体外实验中对胃癌细胞生长、迁移、侵袭的影响。结果:RAC1在胃癌组织中高表达,且不同分化程度、有无局部侵袭、淋巴结转移和不同Lauren’s分型间均有差异(均P<0.05)。RAC1高表达预示了胃癌患者的不良预后。在胃癌细胞中诱导RAC1高表达后发现其在体外促进胃癌细胞的生长、迁移及侵袭(均P<0.05)。使用特异性抑制剂抑制RAC1表达后发现,胃癌细胞生长、迁移及侵袭的生物学功能也受到相应的抑制(均P<0.05)。结论 :RAC1与胃癌的侵袭性相关且是预后不良的指标。体外实验结果也进一步证实了RAC1高表达与胃癌细胞的侵袭性相关,鉴于其在胃癌生长及进展中所起的重要作用,RAC1可作为胃癌治疗的潜在靶点。
Objective To investigate the expression and clinical significance of RAS related C3 botulinum tox substrate1(RAC1) and the role of RAC1 in gastric cancer tumorigenesis and metastasis. Methods The expression of RAC1 in human gastric cancer was detected by immunohistochemistry. The correlation of RAC1 expression with clinicopathological characteristics and survival of patients was analyzed by Pearson's χ2and Kaplan-Meier analyses,respectively. RAC1 overexpression cell model was used to examine in vitro effects of RAC1 on cell growth,migration,and invasion. Results RAC1 was highly expressed in gastric cancer tissue,and was different in relation with differentiation,local invasion,lymph node metastasis,and Lauren's classification. RAC1 overexpression in gastric cancer predicted a shorter survival. In vitro study showed that in gastric cancer cells,overexpression of RAC1 induced would promote cell proliferation,migration and invasion(all P 0.05),and inhibition of RAC1 by specific inhibitor would abrogate these effects(all P 0.05). Conclusions These findings demonstrated that RAC1 was positively correlated with the aggression of gastric cancer and was a factor for poor prognosis. In addition,experimental cell models supported the role of RAC1 in promotion of gastric cancer cell growth,migration and invasion. Given its pivotal role in tumorigenesis and progression,RAC1 could be served as a promising therapeutic target for gastric cancer.
出处
《内科理论与实践》
2015年第5期353-358,共6页
Journal of Internal Medicine Concepts & Practice
关键词
RAC1
胃癌
转移
肿瘤形成
预后
RAC1
Gastric cancer
Metastasis
Tumorigenesis
Prognosis