INHIBITORY EFFECT OF ANTISENSE OLIGONUCLEOTIDE FOR KERATINOCYTE GROWTH FACTOR FAMILY ON COLON CANCER CELLS

目的：探讨成纤维细胞生长因子-7(KGF-7)和成纤维细胞生长因子-10(KGF-2)的反义寡核苷酸对结肠癌细胞生长的抑制作用。材料与方法：采用RT-PCR、免疫组织化学和原位杂交技术检测成纤维细胞生长因子-7、成纤维细胞生长因子-10及其受体(KGFR)在人结肠癌组织和结肠癌细胞系中的表达和定位。将针对成纤维细胞生长因子-7和成纤维细胞生长因子-10的反义寡核苷酸导入结肠癌细胞系，研究其对结肠癌细胞的生长抑制作用。结果与结论：成纤维细胞和结肠癌细胞中均有成纤维细胞和结肠癌细胞表达成纤维细胞生长因子-7和成纤维细胞生长因子-10及其mRNA。KGFR mRNA定位于结肠癌细胞。这些结果表明，成纤维细胞生长因子-7和成纤维细胞生长因子-10可能通过自分泌和旁分泌机制促进结肠癌细胞生长。成纤维细胞生长因子-10反义寡核苷酸抑制结肠癌细胞FOF-10蛋白合成。结论：KGF家族(成纤维细胞生长因子-7、成纤维细胞生长因子-10和KGFR)可能是抑制结肠癌细胞生长的关键因素之一。

PURPOSE : This study was performed to clarify the growth inhibitory effect of antisense oligo-nucleotide of FGF-7 (Keratinocyte Growth Factor, KGF) or FGF-10 (KGF-2) on colon cancer cells.MATERIALS and METHODS : The expression and localization of FGF-7, FGF-10 and their receptor (KGFR) in human colon cancer tissue and colon cancer cell lines were examined using RT-PCR, immunohistochemistry and in situ hybridization. Antisense oligonucleotides for FGF-7 or FGF-10 mRNA were transferred into colon cancer cell lines and the growth inhibitory effect was elucidated.RESULTS and DISCOUSION : FGF-7 and FGF-10 and their mRNAs were localized in fibroblasts and colon cancer cells. KGFR mRNA was localized in colon cancer cells. These findings indicate that FGF-7 and FGF-10 may contribute to colon cancer cell growth via autocrine and paracrine mechanisms. FGF-10 antisense oligonucleotide inhibited the FOF-10 protein synthesis in colon cancer cells. Furthermore the antisense oligonucleotide inhibited the growth of colon cancer cells.CONCLUSION : KGF family (FGF-7,FGF-1O and KGFR) may be one of the key factors for growth inhibitory therapy of colon cancer cells.