【摘要】 目的:探讨HMGB1基因过表达和沉默对子宫内膜癌增殖与侵袭能力的影响及其机制。方法:构建含有HMGB1重组质粒和HMGB1 sh RNA的慢病毒载体并转染人子宫内膜癌HEC-1A,建立过表达和沉默HMGB1基因的HEC-1A细胞株。采用细胞增殖/毒性活性检测试剂盒(cell counting kit-8)、Transwell小室、细胞划痕实验分析HMGB1过表达和沉默对子宫内膜癌HEC-1A细胞生长、增殖、侵袭及转移的影响。采用Western印迹和反转录PCR(reverse transcriptionPCR,RT-PCR)检测过表达和沉默HMGB1后HEC-1A细胞中NF-κB,VEGF及基质金属蛋白酶2(matrix metalloproteinase2,MMP2)的表达情况。结果:过表达HMGB1能够促进子宫内膜癌HEC-1A细胞增殖、侵袭与转移,且HEC-1A细胞中NF-κB,VEGF及MMP2表达上调;干扰HMGB1表达抑制HEC-1A细胞增殖、侵袭与转移,HEC-1A细胞中NF-κB,VEGF及MMP2表达下调。结论:HMGB1与子宫内膜癌增殖、侵袭与转移密切相关,且可能通过NF-κB,VEGF及MMP2影响子宫内膜癌的侵袭与转移;HMGB1可能成为治疗子宫内膜癌的一个重要靶点。更多还原

【Abstract】 Objective: To investigate effects of over-expression and suppression of HMGB1 on proliferation and invasion of endometrial carcinoma HEC-1A cell and underlying mechanisms. Methods: Over-expression or silence of HMGB1 in HEC-1A cell lines were established by lentiviral vector containing HMGB1 recombinant plasmid or by HMGB1 sh RNA, respectively. Cell counting kit-8, Transwell, and wound healing assay were used to analyze proliferation, invasion, and migration of HEC-1A cells, respectively. Western blot and reverse transcription-PCR(RT-PCR) were used to detect the expression of NF-κB, VEGF, and matrix metalloproteinase 2(MMP2) in the cells. Results: Over-expression of HMGB1 promoted the proliferation, invasion, and migration of HEC-1A cell, and up-regulated NF-κB, VEGF, and MMP2 expressions, while suppression of HMGB1 inhibited the proliferation, invasion, and migration of HEC-1A cells and down-regulated NF-κB, VEGF, and MMP2 expressions. Conclusion: HMGB1 plays an important role in proliferation, invasion, and migration of HEC-1A cell via NF-κB/VEGF/MMP2 pathway. HMGB1 might be a potential target for endometrial carcinoma therapy.更多还原