AKR1C3对结肠癌细胞增殖、迁移和侵袭的影响OACSTPCD
Effect of AKR1C3 on proliferation,migration and invasion of colon cancer cells
目的 探究醛固酮类还原酶家族1成员C3(AKR1C3)在结肠癌细胞中的作用及相关分子机制.方法 收集2022年12月至2023年12月150例结肠癌根治术患者的肿瘤标本及相应的癌旁正常肠黏膜组织标本,分析AKR1C3表达水平与结肠癌临床病理特征的关系.采用GEPIA2数据库分析不同AKR1C3表达结肠癌患者Kaplan-Meier生存曲线.①将SW620细胞分为对照组、LV-NC组、LV-AKR1C3组和PD98059组(PD98059为ERK抑制剂);②将SW620细胞分为对照组、si-NC组、si-AKR1C3组和TBHQ组(TBHQ为ERK激活剂).采用MTT法检测细胞增殖活性,划痕愈合实验检测细胞迁移,Transwell小室实验检测细胞侵袭,qRT-PCR实验检测细胞中AKR1C3基因表达水平,Western blot实验检测细胞中AKR1C3、ERK1/2、p-ERK1/2、c-Jun和p-c-Jun蛋白表达水平.结果 与癌旁组织比较,AKR1C3的mRNA和蛋白在结肠癌肿瘤组织中均升高(P<0.05),AKR1C3低表达患者生存期明显优于AKR1C3高表达患者(P=0.03).AKR1C3表达水平与肿瘤大小、分化程度、浸润程度和淋巴结转移情况具有相关性(P<0.05).与LV-NC组比较,LV-AKR1C3组SW620细胞中AKR1C3的mRNA和蛋白表达水平以及ERK1/2和c-Jun蛋白磷酸化水平均升高(P<0.05),细胞增殖活性、相对迁移率和侵袭数量均升高(P<0.05);与LV-AKR1C3组比较,PD98059组细胞中AKR1C3的mRNA和蛋白表达水平以及ERK1/2和c-Jun蛋白磷酸化水平均降低(P<0.05),细胞增殖活性、相对迁移率和侵袭数量均降低(P<0.05).与si-NC组比较,si-AKR1C3组SW620细胞中AKR1C3的mRNA和蛋白表达水平以及ERK1/2和c-Jun蛋白磷酸化水平均升高(P<0.05),细胞增殖活性、相对迁移率和侵袭数量均降低(P<0.05);与LV-AKR1C3组比较,TBHQ组细胞中AKR1C3的mRNA和蛋白表达水平以及ERK1/2和c-Jun蛋白磷酸化水平均降低(P<0.05),细胞增殖活性、相对迁移率和侵袭数量均升高(P<0.05).结论 AKR1C3在结肠癌中高表达,AKR1C3通过激活ERK/c-Jun信号通路促进结肠癌细胞增殖、迁移和侵袭.
Objective To explore the role of AKR1C3 in colon cancer cells and its related molecular mechanism.Methods Tumor tissue specimens and their corresponding adjacent normal intestinal mucosal tissue specimens of 150 patients undergoing radical resec-tion of colon cancer in our hospital from December 2022 to December 2023 were collected to analyze the relationships between AKR1C3 expression level and the clinicopathological features of colon cancer.The survival of colon cancer patients with different AKR1C3 expression was anlyzed based on GEPIA2 database by Kaplan-Meier survival curve.SW620 cells were divided into control group,LV-NC group,LV-AKR1C3 group and PD98059(an ERK inhibitor)group.SW620 cells were divided into control group,si-NC group,si-AKR1C3 group and TBHQ(an ERK activator)group.The proliferation activity of cells was detected by MTT.The migration ability of cells was detected by scratch healing assay.The invasion ability of cells was detected by Transwell assay.The mRNA expression le-vels of AKR1C3 in SW620 cells were detected by qRT-PCR.The protein expression levels of AKR1C3,ERK1/2,p-ERK1/2,c-Jun and p-c-Jun in cells were detected by Western blot.Results Compared with paracancer tissue,the mRNA and protein expressions of AKR1C3 in colon cancer tumor tissues were increased(P<0.05),and the survival of patients with low expression of AKR1C3 was significantly higher than that of patients with high expression of AKR1C3(P=0.03).The expression level of AKR1C3 was correlated with tumor size,differentiation,invasion and lymph node metastasis(P<0.05).Compared with LV-NC group,the mRNA and protein expression levels of AKR1C3 and the protein phosphorylation levels of ERK1/2 and c-Jun were increased in LV-AKR1C3 group(P<0.05),and the cell proliferation activity,the relative migration rate and the invasion cell number were increased(P<0.05).Compared with LV-AKR1C3 group,the mRNA and protein expression levels of AKR1C3 and the protein phosphorylation levels of ERK1/2 and c-Jun were decreased in PD98059 group(P<0.05),and the cell proliferation activity,the relative migration rate and the invasion cell number were decreased(P<0.05).Compared with si-NC group,the mRNA and protein expression levels of AKR1C3 and protein phos-phorylation levels of ERK1/2 and c-Jun were increased in si-AKR1C3 group(P<0.05),while the cell proliferation activity,the relative migration rate and the invasion cell number were decreased(P<0.05).Compared with LV-AKR1C3 group,the mRNA and protein ex-pression levels of AKR1C3 and the protein phosphorylation levels of ERK1/2 and c-Jun were decreased in TBHQ group(P<0.05),while the cell proliferation activity,the relative migration rate and the invasion cell number were increased(P<0.05).Conclusion AKR1C3 is highly expressed in colon cancer,and AKR1C3 could promote the proliferation,migration and invasion of colon cancer cells by activating the ERK/c-Jun signaling pathway.
王娜;郭晓冉;牛学敏
石家庄市人民医院消化内科,石家庄 050030石家庄市人民医院驻第二看守所门诊部石家庄市人民医院消化内科,石家庄 050030
临床医学
AKR1C3ERK/c-Jun结肠癌增殖迁移侵袭
Aldo-keto reductase family 1 member C3(AKR1C3)ERK/c-Juncolon cancerproliferationmigrationinvasion
《山西医科大学学报》 2024 (10)
1269-1278,10
河北省医学科学研究课题计划项目(20221693)石家庄市科技计划项目(221460443)
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