HOXA4调控Wnt/β-catenin信号通路对裸鼠移植胶质瘤的抑制作用

doi:10.13481/j.1671-587x.20190302

Abstract

Abstract: Objective:To establish the glioma-bearing nude mouse models, and to investigate the effect of HOXA4 on the growth of glioma U251 cells in vivo and its regulatory effect on the Wnt/β-catenin signal pathway and its mechanism. Methods:The glioma U251 cell line stably transfected with HOXA4 siRNA(si-HOXA4) and the U251 cell line stably transfected with blank vector (si-NC) were established by lentivirus transfection. The U251, si-NC, and si-HOXA4 cells were respectively inoculated under the skin of the neck and back of the BALB/c nude mice to establish the glioma-bearing nude mouse models named as control group, si-NC group, and si-HOXA4 group. The tumorigenesis of nude mice in various groups were observed and the tumor growth curve was drawn. The tumor tissue was stripped after the mice were sacrificed on the 21 th day, and the volume and weight of tumor were measured; the relative mRNA expression amounts of HOXA4, CTNNB1, and Gsk3β in tumor tissue of the nude mice in various groups were detected by qRT-PCR method; the expression levels of HOXA4, β-catenin, Gsk3β, CyclinD1, and P53 proteins in tumor tissue of the nude mice in various groups were detected by immunohistochemistry (IHC) method. Results:Compared with si-NC group and control group, the volume and weight of tumor of the nude mice in si-HOXA4 group were significantly decreased(P<0.05). The relative expression amount of HOXA4 mRNA and the expression level of HOXA4 protein in si-HOXA4 group were significantly lower than those in the other groups (P<0.05). Compared with si-NC group and control group, the relative expression amount of CTNNB1 mRNA and the expression levels of β-catenin and CyclinD1 proteins in si-HOXA4 group were significantly decreased (P<0.05), and the expression levels of Gsk3β and P53 proteins were significantly increased (P<0.05). Conclusion:Inhibition of HOXA4 expression in human glioma U251 cells can regulate the expressions of CyclinD1 and P53 through Wnt/-catenin signal pathway in vivo, thus inhibiting the tumor growth of glioma-bearing nude mice.

Key words: glioma, homeobox gene A4, Wnt/β-catenin, signal pathway, nude mice, CyclinD1, P53

CLC Number:

R739.4

ZHOU Haixia, HOU Lijian, WANG Zhengming, TIAN Yu, HAN Liang, LI Mifu. Inhibitory effect of HOXA4 on transplantationglioma of nude mice through regulating Wnt/β-catenin signal pathway[J].Journal of Jilin University(Medicine Edition), 2019, 45(03): 474-478.

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Inhibitory effect of HOXA4 on transplantationglioma of nude mice through regulating Wnt/β-catenin signal pathway

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