SIX2在骨肉瘤组织中表达及其对细胞血管生成与阿霉素耐药逆转的影响  

Expression of SIX2 in osteosarcoma and its effect on angiogenesisand reversal of doxorubicin resistance

作　　者：王熠欣 张世才 黄海燕 陈晨 张斯 刘颖 王有南 WANG Yixin;ZHANG Shicai;HUANG Haiyan;CHEN Chen;ZHANG Si;LIU Ying;WANG Younan(Fengfeng General Hospital,North China Medical,Health Group,Handan 056201,Hebei,China)

机构地区：[1]华北医疗健康集团峰峰总医院,河北邯郸056201

出　　处：《西部医学》2023年第8期1104-1109,共6页Medical Journal of West China

基　　金：河北省医学科学研究课题(20222397)。

摘　　要：目的 探究SIX2在骨肉瘤组织中表达及其对细胞血管生成与阿霉素耐药逆转的影响。方法 收集2019年3月—2021年12月我院行骨肉瘤手术切除的105例患者的组织标本,免疫组化检测骨肉瘤组织中SIX2表达和微血管密度(MVD)计数;检测骨肉瘤组织中SIX2 mRNA表达水平。将人骨肉瘤细胞系MG-63分为MG-63组、si-NC A组、si-SIX2 A组,将通过阿霉素耐药得到的骨肉瘤阿霉素耐药细胞株MG-63/R分为MG-63/R组、si-NC B组和si-SIX2 B组。分别用MTT法、克隆实验、流式细胞术及Transwell法检测细胞耐药性、细胞增殖、细胞凋亡和细胞侵袭。结果 在骨肉瘤组织中,SIX2阳性表达会随着MVD值升高而增加(P<0.05)。骨肉瘤组织中SIX2阳性表达与TNM分期、软组织浸润和淋巴结远处转移相关(P>0.05)。与MG-63组相比,si-SIX A组细胞的血管形成能力明显降低(P<0.05);与MG-63/R组相比,si-SIX2 B组细胞IC50、细胞克隆数和细胞侵袭能力均显著降低,细胞凋亡能力明显增加,细胞耐药指数逆转倍数为2.51倍(P<0.05)。结论 SIX2在骨肉瘤组织中呈高表达,且随着SIX2表达的升高肿瘤血管生成能力也增加;抑制SIX2表达可有效抑制骨肉瘤组织的生成,逆转骨肉瘤细胞阿霉素耐药。Objective To investigate the expression of SIX2 in osteosarcoma and its effect on angiogenesis and reversal of doxorubicin resistance.Methods Tissue specimens of 105 patients who underwent surgical resection of osteosarcoma in our hospital from March 2019 to December 2021 were collected.SIX2 expression and microvascular density(MVD)count in osteosarcoma were detected by immunohistochemistry.The expression level of SIX2 mRNA in osteosarcoma was detected.Human osteosarcoma cell line MG-63 was divided into MG-63 group,si-NA group,si-SIX2A group.Adriamycin-resistant osteosarcoma cells MG-63/R were divided into MG-63/R group,si-NB group and si-SIX2B group.MTT assay,cloning assay,flow cytometry and Transwell assay were used to detect cell resistance,cell proliferation,cell apoptosis and cell invasion.Results In osteosarcoma tissue,the positive expression of SIX2 increased with the increase of MVD value(P<0.05).The positive expression of SIX2 in osteosarcoma tissue was correlated with TNM stage,soft tissue infiltration and distant lymph node metastasis(P>0.05).Compared with MG-63 group,the angiogenesis ability of cells in si-SIXA group was significantly decreased(P<0.05).Compared with MG-63/R group,the IC50,cell clone number and cell invasion ability of si-SIX2 B group cells were significantly decreased,the apoptotic capacity was significantly increased,and the reversal fold of the cell resistance index was 2.51 times(P<0.05).Conclusion SIX2 was highly expressed in osteosarcoma tissues,and the tumor angiogenesis ability also increased with the increase of SIX2 expression.Inhibition of SIX2 expression can effectively inhibit the formation of osteosarcoma tissue and reverse the doxorubicin resistance of osteosarcoma cells.

关 键 词：SIX2 骨肉瘤组织 细胞血管生成 阿霉素耐药逆转 

分 类 号：R738.7[医药卫生—肿瘤]