壮观霉素B1抑制SUMO化修饰遏制子宫内膜癌侵袭和转移  

Spectinomycin B1 inhibits protein small ubiquitin-like modified protein modification and prevents invasion and metastasis of endometrial cancer

作　　者：袁梦岚[1] 李承尧 白洁 陈旭红[1] 刘晓智[3] 李圃[2] YUAN Meng-lan;LI Cheng-yao;BAI Jie;CHEN Xu-hong;LIU Xiao-zhi;LI Pu(Department of Obstetrics and,Gynecology,Tianjin Fifth Central Hospital,Tianjin 300450,China;不详)

机构地区：[1]天津市第五中心医院妇产科,天津300450 [2]天津市中心妇产科医院妇产科,天津300052 [3]天津市第五中心医院天津市早产儿器官发育表观遗传重点实验室,天津300450

出　　处：《广东医学》2022年第2期169-173,共5页Guangdong Medical Journal

基　　金：天津市科技计划项目(18ZXZNSY00260);天津市卫生健康委员会科技项目(ZC20140)。

摘　　要：目的观察壮观霉素B1能否通过抑制蛋白质类泛素化修饰途径抑制子宫内膜癌的侵袭和转移,为子宫内膜癌的靶向治疗提供依据。方法以子宫内膜癌KLE细胞株为研究对象,分对照组及壮观霉素B1组;细胞增殖检测试剂盒检测5-乙炔基-2′-脱氧尿苷(EdU)的阳性表达率;细胞划痕实验及Transwell侵袭实验检测细胞迁移和侵袭能力;Western blotting方法检测泛素连接酶-9(Ubc9)、小泛素样修饰蛋白-1(SUMO1)、基质金属蛋白酶-9(MMP-9)和MMP-13的蛋白表达情况。结果对照组及壮观霉素B1组KLE细胞中EdU的阳性表达率分别为(94.46±4.27)%和(51.33±5.08)%(t=12.654,P<0.01);细胞迁移距离分别为(44.15±4.07)μm和(22.74±3.95)μm(t=14.359,P<0.01);高倍视野下自Transwell上室向下室迁移的细胞数分别为(67.05±6.54)个和(36.44±4.05)个(t=11.997,P<0.01);壮观霉素B1组KLE细胞中Ubc9、SUMO1、MMP-9和MMP-13的蛋白表达均明显低于对照组,差异有统计学意义(P<0.05)。结论壮观霉素B1能够明显抑制蛋白质SUMO化修饰反应,进而影响子宫内膜癌迁移和侵袭相关责任蛋白的表达,有望成为一种靶向治疗子宫内膜癌的新方法。Objective To observe whether spectinomycin B1 could inhibit the invasion and metastasis of endometrial cancer by inhibiting small ubiquitin-like modified protein(SUMO) modification, and to provide basis for targeted therapy of endometrial cancer. Methods The KLE cell line of endometrial cancer was used as the research object. Cells were divided into control group and spectinomycin B1 group. The cell proliferation detection kit was used to detect the positive expression rate of 5-ethynyl-2′-deoxyuridine(EdU). Cell scratch test and Trans-well invasion test were used to detect cell migration and invasion ability. Western blotting method was applied to assess the protein expression of ubiquitin ligase-9(Ubc9), small ubiquitin-like modified protein-1(SUMO1), matrix metalloproteinase-9(MMP-9) and MMP-13. Results In KLE cells in the control group and spectinomycin B1 group, the positive expression rates of EdU were(94.46±4.27)% and(51.33±5.08)%, respectively(t=12.654, P<0.01);the cell migration distances were(44.15±4.07)μm and(22.74±3.95)μm, respectively(t=14.359, P<0.01);and the number of cells that migrated from the upper chamber of Trans-well to the lower chamber under high power field was 67.05±6.54 and 36.44±4.05, respectively( t=11.997, P<0.01). The level of Ubc9, SUMO1, MMP-9 and MMP-13 proteins in KLE cells in the Spectinomycin B1 group were significantly lower than those of the control group(P<0.05). Conclusion Spectinomycin B1 can significantly inhibit the protein SUMO modification, thereby affecting the expression of responsible proteins related to endometrial cancer migration and invasion, and is expected to become a new method for targeted treatment of endometrial cancer.

关 键 词：子宫内膜癌 壮观霉素B1 小泛素样修饰蛋白 侵袭 转移 

分 类 号：R737.33[医药卫生—肿瘤] R392.5[医药卫生—临床医学]