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Raf激酶抑制蛋白对肝癌细胞生物学特性的影响及其潜在治疗作用。

Effects of Raf kinase inhibitor protein on biological characteristics of hepatocellular carcinoma cells and its potential therapeutic effects.

作者信息

Lin Zhang, Jianhua Zhu, Kai Wu, Yanhong Hou, Haorun Liu

机构信息

Department of Gastroenterology, Eighth Medical Center, General Hospital of Chinese PLA, Beijing 100091, China.

出版信息

ILIVER. 2022 Nov 22;1(4):275-282. doi: 10.1016/j.iliver.2022.11.005. eCollection 2022 Dec.

Abstract

BACKGROUND AND AIMS

Raf kinase inhibitor protein (RKIP) is an important member of the phosphatidylethanolamine-binding protein family. This study investigated the inhibitory effect of RKIP on the malignant biological behavior of liver cancer cells in vivo and in vitro.

METHODS

An RKIP gene expression vector was constructed using the pcDNA3.1 vector and transfected into human hepatoma cell line HepG2 to overexpress the RKIP gene. Growth, proliferation, the cell cycle, apoptosis, migration, and invasion of the cell line were analyzed. For in vivo experiments, the vector was transfected into tumor tissue of hepatoma-bearing animals and then tumor growth was analyzed and compared with the control to assess its anti-tumor effect.

RESULTS

Compared with the control group, cell growth in the RKIP gene transfection group (HEP-RKIP) was significantly slower. The average colony formation rate of the HEP-RKIP group was significantly lower than that of the other two groups ( < 0.05). The proportion of HEP-RKIP cells in G0/G1 phase was significantly higher than that of the control group ( < 0.05), while the proportion of cells in G2/M phase was significantly lower than that in the control group ( < 0.05). The apoptosis rate of HEP-RKIP cells was approximately 6.4%, which was significantly higher than that of the control group ( < 0.05). Migration of HEP-RKIP cells was significantly slower than that of the other two groups ( < 0.05). In an inhibition experiment of the liver tumor animal model, the tumor inhibition rate of the RKIP in vivo transfection group was significantly higher than that of each control group ( < 0.05).

CONCLUSION

RKIP inhibits malignant biological behavior of liver cancer cells in vitro and has a tumor inhibitory effect in vivo, which may be a potential target for gene therapy of liver cancer.

摘要

背景与目的

Raf激酶抑制蛋白(RKIP)是磷脂酰乙醇胺结合蛋白家族的重要成员。本研究探讨RKIP对肝癌细胞体内外恶性生物学行为的抑制作用。

方法

利用pcDNA3.1载体构建RKIP基因表达载体,并转染至人肝癌细胞系HepG2中,以过表达RKIP基因。分析该细胞系的生长、增殖、细胞周期、凋亡、迁移及侵袭情况。在体内实验中,将该载体转染至荷肝癌动物的肿瘤组织,然后分析肿瘤生长情况,并与对照组比较以评估其抗肿瘤作用。

结果

与对照组相比,RKIP基因转染组(HEP-RKIP)细胞生长明显减慢。HEP-RKIP组的平均集落形成率显著低于其他两组(P<0.05)。HEP-RKIP细胞G0/G1期比例显著高于对照组(P<0.05),而G/M期细胞比例显著低于对照组(P<0.05)。HEP-RKIP细胞凋亡率约为6.4%,显著高于对照组(P<0.05)。HEP-RKIP细胞迁移明显慢于其他两组(P<0.05)。在肝肿瘤动物模型抑制实验中,RKIP体内转染组肿瘤抑制率显著高于各对照组(P<0.05)。

结论

RKIP在体外抑制肝癌细胞的恶性生物学行为,在体内具有肿瘤抑制作用,可能是肝癌基因治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e377/12212733/ed1f232722fb/gr1.jpg

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