Targeting blockage of Wnt signal transduction pathway of nm23-H1 gene transfection in human high-metastatic large cell lung cancer cell line L9981 / 中国肺癌杂志

ABSTRACT

<p><b>BACKGROUND</b>To explore the possibility of targeting blockage of Wnt signal transduction pathway of nm23-H1 gene transfection in human high-metastatic large cell lung cancer cell line L9981, and to provide evidence to elucidate the signal conductive mechanism of nm23-H1 mediated tumor metastasis suppression.</p><p><b>METHODS</b>The expression of GSK-3β and β-catenin of Wnt signal pathway was detected in cytoplasm and nucleus in L9981 cell line with nm23-H1 deletion, L9981-pLXSN cell line transfected with vector and L9981-nm23-H1 cell line transfected with nm23-H1 gene by Western blot.</p><p><b>RESULTS</b>(1)GSK-3β expression in L9981-nm23-H1 cytoplasm (6 341±541) was significantly higher than those in L9981 (3 736±298) and L9981-pLXSN (3 613±383) cell lines ( P < 0.001); (2)GSK-3β expression in L9981-nm23-H1 nucleus (4 356±490) was significantly higher than those in L9981 (657±57) and L9981-pLXSN (705±75) cell lines ( P < 0.001); (3)β-catenin expression in L9981-nm23-H1 cytoplasm (3 649±118) was significantly higher than those in L9981 (1 401±31) and L9981-pLXSN (1 350±55) cell lines ( P < 0.001); (4)No statistical difference of the β-catenin expression in nucleus was observed among L9981-nm23-H1 (2 945±68), L9981 (2 604±23) and L9981-pLXSN (2 652±53)( P > 0.05); (5)No significant difference of GSK-3β or β-catenin expression in cytoplasm and nucleus was observed between L9981 and L9981-pLXSN ( P > 0.05).</p><p><b>CONCLUSIONS</b>(1)nm23-H1 gene can remarkably upregulate the expression of GSK-3β in cytoplasm and nucleus, and β-catenin expression in cytoplasm in L9981-nm23-H1 cell, but can not induce the nucleus accumulation of β-catenin. (2)Regulation of GSK-3β and β-catenin expression, and targeting blockage of Wnt signaling pathway may be one of molecular mechanisms that nm23-H1 contributes to play a vital role in the "Lung Cancer Metastasis Suppressive Cascade".</p>