奥曲肽下调cMet的表达抑制肝细胞癌的生长

目的 研究生长抑素类似物奥曲肽对肝细胞癌生长的影响及其抑瘤机理。方法 以MTT法检测奥曲肽对Bel7402人肝癌细胞株增殖的影响,光镜下观察细胞形态的变化;以细胞“划痕”实验和黏附实验观察其对细胞侵袭和黏附能力的影响;以流式细胞仪检测细胞周期及细胞表面肝细胞生长因子受体cMet表达的变化。以裸鼠人肝癌转移模型为材料,观察奥曲肽对种植瘤生长的影响及其预防种植瘤切除术后复发转移的作用,免疫组化法观察种植瘤内cMet蛋白表达。结果 奥曲肽处理后的Bel7402细胞增殖能力和细胞形态无明显改变;细胞的侵袭和黏附能力随着奥曲肽作用时间的延长明显低于未经奥曲肽处理的Bel7402细胞株（P〈0．05）;处于生长静止期（G0／G1）细胞的比例显著增加（P〈0．01）;cMet表达阳性的细胞比例明显减少（P〈0．001）。裸鼠人肝癌种植瘤的生长受到明显抑制（P〈0．001）,奥曲肽的抑瘤率为67．9％,种植瘤内cMet的阳性表达程度也显著降低;同时,种植瘤切除后无一例出现复发转移,而未经奥曲肽处理者,有3例复发且其中1例死亡,肝内转移瘤内cMet表达亦高于原种植瘤,但差异无统计学意义。结论 奥曲肽能通过下调cMet的表达抑制肝癌的生长。

Octreotide Inhibits the Growth of Hepatocellular Carcinoma Through Down-Regulation of cMet

Objective To investigate the inhibitory effects and the mechanisms of octreotide(OCT) on the growth of hepatocellular carcinoma(HCC).Methods Bel7402 HCC cells were studied for proliferative ability by MTT assay,morphology by light microscopy,adhesive and invasive ability by cell adhesion and "wound strack" experiments.Immunofluorescence flow cytometry was used for study of cMet expression and cell cycle as well. Furthermore,the effects of OCT on tumor growth metastasis were investigated in nude mice with implanted HCC.The expression of cMet in implanted tumor cells was studied by immunohistochemistry.Results With OCT treatment,the proliferative ability of Bel7402 cells and cell morphology didn't change.The adhesive and invasive ability decreased compared with no OCT treatment cells(P<0.05).The ratio of G_0/G_1 cells increased markedly (P<0.05).The proportion of Bel7402 cells expressing cMet was reduced significantly(P<0.05).The growth of implanted tumor was inhibited with OCT treatment(P<0.05).The intensity of cMet expression in OCT group was remarkably weaker than that in control group.In addition,no recurrence and metastasis was found in OCT group 7 weeks after curative resection of xenografts,while 3 cases in controd group were observed to have the recurrence and metastasis.The intensity of cMet immunolabeling in the metastatic tumors was higher than that in xenografts of control group,but the difference was not significant.Conclusion OCT inhibits the growth of HCC by down-regulation of cMet.