GM6001对宫颈鳞癌HCE1多细胞球体浸润 人脐静脉内皮细胞的影响

目的：探讨基质金属蛋白酶(MMP)-9在宫颈鳞癌HCE1多细胞球体中的表达与宫颈癌浸润的关系，研究MMP抑制剂GM6001对HCE1多细胞球体浸润人脐静脉内皮细胞（HUVECs）的影响。方法：建立宫颈鳞癌HCE1多细胞球体浸润HUVECs模型；采用免疫组织化学法检测宫颈鳞癌HCE1单层细胞、多细胞球体MMP-9的表达；光镜下观察GM6001（2.5，12.5 μmol/L）干预宫颈鳞癌HCE1多细胞球体浸润模型的形态学改变并检测干预后HCE1浸润模型中MMP-9的表达。结果：成功建立HCE1浸润模型；HCE1多细胞球体中MMP-9的阳性表达率明显高于HCE1单层细胞（P＜0.05）；与对照组比较，GM6001低剂量组和高剂量组HCE1多细胞球体浸润能力抑制率分别为26.09%和92.95%(P＜0.05)，其浓度增加抑制能力增强；宫颈鳞癌HCE1多细胞球体浸润模型（第4天）GM6001高剂量组HCE1多细胞球体中MMP-9表达较对照组明显下调（χ2=7.033,P＜0.05）。结论：HCE1多细胞球体的浸润能力增强，可能与多细胞球体中MMP-9表达上调有关； GM6001可以下调HCE1多细胞球体中MMP-9的表达，部分阻断HCE1多细胞球体对单层HUVECs的浸润作用。

Effect of GM6001 on the model that cervical squamous carcinoma cell line HCE1 multicellular spheroids invade live human umbilical vein endothelium cell monolayers

ObjectiveTo investigate the relationship between matrix matrix metalloproteinases(MMP)-9 expression in HCE1/multicellular spheroids (MCS) and invasion of cervical carcinoma, and to explore the effect of MMPs inhibitor GM6001 on the model that HCE1/MCS invade live human umbilical vein endothelium cell (HUVEC).MethodsWe established the invasion model by coculturing HCE1/MCS and HUVEC, and detected the MMP-9 expression in HCE1 monolayer cells (HCE1/MC), HCE1/MCS and HUVEC using immunohistochemistry and treated the HCE1/MCS invasion model with GM6001. ResultsA cervical squamous carcinoma cell HCE1 infiltrating model was established. Compared with that in HCE1/MC, MMP-9 expression in the HCE1/MCS was significantly higher (P＜0.05). Compared with the control group, the invasion of HCE1/MCS was inhibited by 26.09 % and 92.95%(P＜0.05) in the GM6001 2.5 μmol/L and 12.5 μmol/L group. MMP-9 expression in HCE1/MCS in the GM6001 12.5 μmol/L group was obviously lower than that in the control group (P＜0.05). With the increase of the concentration of GM6001, the inhibition increased. ConclusionThe enhancement of HCE1/MCS invasion may be related to the up-regulation of MMP-9 expression in HCE1/MCS. GM6001 can down regulate the MMP-9 expression in HCE1/MCS and partially block the HCE1/MCS invasion to HUVEC.