奥曲肽抑制转化生长因子α诱导肝癌细胞增殖的实验研究

Experimental study of the inhibitory effect of octreotide on transforming growth factor-alpha-induced proliferation of human hepatocellular carcinoma cells

摘要:

目的：探讨奥曲肽对转化生长因子α(TGF-α)诱导肝癌细胞增殖的抑制作用及其机制。
方法：用免疫组化法观察奥曲肽对TGF-α诱导肝癌细胞增殖的影响，用逆转录-聚合酶链反应(RT-PCR)检测奥曲肽对肝癌细胞TGF-α分泌和表皮生长因子受体(EGFR)表达的影响，用Western-blot法、免疫组化法检测奥曲肽对细胞外信号调节蛋白激酶 (ERK)的影响。
结果：奥曲肽明显抑制细胞核内TGF-α诱导的增殖细胞核抗原(PCNA)表达，使肝癌细胞TGF-αmRNA指数较对照组降低(P<0.05)，对TGF-α诱导的EGFRmRNA指数的增加具有明显抑制作用。Western-blot显示，奥曲肽明显抑制TGF-α诱导的ERK蛋白表达;免疫组化显示，TGF-α作用后，胞核染色明显加深，奥曲肽与TGF-α同时作用后胞核染色明显减弱。
结论：奥曲肽可能通过抑制肝癌细胞分泌TGF-α，抑制EGFR表达和阻断EGFR信号传导，从而抑制TGF-α诱导的肝癌细胞增殖。

Abstract:

Abstract:Objective：To investigate the inhibitory effect of octreotide on transforming growth factor-alpha (TGF-α)-induced cell proliferation of human hepatocellular carcinoma cells and its possible mechanism.
Methods ：The effect of octreotide on TGF-α-induced cell proliferation of the liver cancer cells (LCC) was evaluated by immunohistochemistry method. The effect of octreotide on TGF-α secretion and epidermal growth factor receptor(EGFR) expression in the cells was determined by reverse-transcriptase polymerase chain reaction(RT-PCR). The effect of octreotide on extracellular signal-regulated protein kinase (ERK) expression in the cells was measured by Western-blot and immunohistochemistry method.
Results：The TGF-α-induced expressions of proliferating cell nuclear antigen (PCNA) in nucleus were obviously increased by TGF-α. TGF-αmRNA index of hepatocellular carcinoma cells was decreased by octreotide. Octreotide inhibited significantly the expressions of EGFR mRNA induced by TGF-α. Octreotide inhibited significantly the expressions of ERK protein induced by TGF-α. There was intense staining in the nucleus of the cells by TGF-α and weak staining in the nucleus of the cells treated simultaneously by octreotide and TGF-α.
Conclusions：Octreotide can inhibit the secretion of TGF-α, the expression of EGFR, and the signal transduction of EGFR of LCC, and consequently exerts an inhibitory effect on TGF-α-induced hepatocellular carcinoma cells proliferation.