抑制P18^INK4C表达对胃腺癌细胞侵袭的影响

应用基因芯片技术筛选胃腺癌转移相关基因的过程中 ,发现CDK抑制因子 (CKI)P18INK4C在人类胃腺癌转移细胞株RF 4 8中的表达 ,较其原发灶细胞株RF 1明显下调。这提示 ,P18INK4C表达差异与胃腺癌细胞的侵袭转移 ,可能有一定程度的相关性。为此 ,通过反义RNA技术抑制在RF 1中的表达 ,研究其对胃腺癌原发灶细胞体外运动、侵袭转移能力以及生长特性的影响 ,进一步明确P18INK4C与人类胃腺癌侵袭转移之间的关系。结果发现 ,抑制P18INK4C的表达 ,可以使胃腺癌原发灶细胞的体外侵袭能力明显增加 ,抑制前RF 1细胞的体外侵袭能力仅为抑制后的 4 4 %。然而 ,RF 1的细胞周期和生长增殖能力 ,并未因为P18INK4C表达的改变而受到影响。上述结果提示 ,P18INK4C参与人类胃腺癌转移过程 ;在此过程中 ,其主要的作用可能并不是调节细胞周期 ,而是与胃腺癌原发灶细胞侵袭转移能力的调节密切相关。

The Effects of Inhibiting P18 ~ (INK4C) Expression on the Invasion of Gastric Adenocarcinoma Cell Line

Using cDNA microarray with double dots of 4096 human genes, P 18 INK4C, a member of CKI, was found down-regulated in a gastric adenocarcinoma metastatic cell line (RF-48), compared with the corresponding primary cancer cell line (RF-1), which implied that P18 INK4C might be involved in cell invasion and metastatic progression of human gastric adenocarcinoma. Antisense RNA expression plasmid was applied to inhibit P18 INK4C expression to study the effect of decreased P18 INK4C expression on cell migration, invasion and proliferation ability and cell cycle of RF-1. Results showed that inhibition of P18 INK4C expression could obviously enhance cell invasion ability of RF-1, but had little effect on its cell cycle and cell migration and proliferation ability. These results implied that P18 INK4C might play a pivotal role in regulating cell invasion, rather than regulating cell cycle and proliferation in the progression of human gastric adenocarcinoma as expected before.