促肝再生磷酸酶-3在胃癌患者组织中的表达及其对胃癌细胞生长的影响

目的 评价促肝再生磷酸酶-3(PRL-3)高表达对胃癌预后的影响及沉默PRL-3表达对SGC7901细胞增殖及移植瘤生长的影响.方法 免疫组化法检测137例胃癌标本中PRL-3的表达;Log-rank检验比较PRL-3高表达患者与非PRL-3高表达患者的总体生存率.构建表达人工PRL-3miRNA的慢病毒载体,转染SGC7901细胞并沉默其PRL-3表达,MTT试验评价对SGC7901细胞增殖的影响,移植瘤生长试验评估对胃癌生长的抑制作用.结果 137例原发灶组织中,85例(62%)为PRL-3高表达;26例(19%)为PRL-3中度表达;26例(19%)为PRL-3低表达.PRL-3高表达与胃癌肿瘤大小(P<0.01)、浸润深度(P<0.01)、淋巴结转移(P<0.01)、肝转移(P<0.01)、周围脏器侵犯(P<0.01)及临床TNM分期(P<0.01)显著相关.PRL-3高表达患者的总体生存率显著低于PRL-3中等度或低度表达的患者(P<0.01).与转染空载体组比较,转染PRL-3 miRNA的慢病毒载体可抑制SGC7901细胞的增殖.荷瘤动物实验表明,转染PRL-3组肿瘤大小为(1.92±0.18)cm3,转染空载体组肿瘤大小为(4.74±0.39)cm3(P<0.01).结论 PRL-3的高表达与胃癌恶性进展有关,沉默PRL-3表达可抑制胃癌SGC7901细胞的增殖,并抑制移植瘤的生长.PRL-3胃癌生长中起着关键作用,可作为胃癌潜在的治疗靶点.

Expression of phosphatase of regenerating liver-3 in gastric cancer, its relationship with prognosis, and its role in gastric cancer cell proliferation

Objective To detect the expression of phosphatase of regenerating liver (PRL)-3 in primary gastric cancer tissues, evaluate its prognostic impact, and investigate the role of silencing PRL-3 expression by miRNA interference in gastric cancer growth. Methods Immunohistochemistry was used to measure the expression of PRL-3 in 137 gastric tumor samples. The overall survival rates of the patients with different PRL-3 expression levels were compared. Recombinant lentivirus expressing artificial PRL-3 miRNA, Lent. rPRL3-miRs, was established. Human gastric cancer ceils of the line SGC7901 were cultured and transfected with Lent. rPRL3-miRs or blank vector, Lenti. rPRL-miR-neg, respectively. Un-transfected progenitor cells were used as controls. MTT assay was used to examine the proliferation of these cells. RTPCR and Western blotting were used to detect the RNA and protein expression of PRL-3 in the SGC7901 cells. Thirty BALB/c mice were divided into 3 equal groups to be inoculated subcutaneously with SGC7901 ceils transfected with Lent. rPRL3-miRs or blank vector, and control SGC7901 ceils respectively. The growth of tumor was observed and the tumor sizes were measured 21 days later. Results 85 of the 137 gastric cancer samples (62%) showed high PRL-3 expression and 26 (19%) showed moderate and low PRL-3 expression. High PRL-3 expression was significantly correlated with tumor size ( P< 0. 01 ), infiltration depth (P< 0. 01 ), lymph node metastasis ( P< 0. 01 ), hepatic metastasis ( P< 0. 01 ), adjacent organ invasion ( P< 0. 01 ), and TNM staging ( P< 0. 01 ). The median survival time of the patients with high PRL-3 expression in the primary tumor was 18.9 months, significantly shorter than those with moderate or low expression (39.1 and 74.3 months respectively, both P< 0. 01 ). The growth rate of the SGC7901 cells transfected with the recombinant lentivirus expressing artificial PRL-3 miRNA was significantly lower than that of the blank vector-transfected group. The implanted tumor size of the Lenti. rPRL-3-miR-B transfection group was ( 1.92 ±0. 18 ) cm3, significantly smaller than those of the control and Lenti. rPRL-miR-neg groups [(4.86±0.38) and(4.74±0.39)cm3 respectively, both P<0.01]. Conclusion High PRL-3 expression is associated with gastric cancer progression. Silencing of PRL-3 significantly suppresses the proliferation of gastric cancer cells and tumor growth. PRL-3 plays a key role in the growth of gastric cancer. PRL-3 should be considered as a potential therapeutic target.