bFGF及TPK抑制剂对听神经瘤细胞增殖的影响

Effects of bFGF and TPK inhibitor-genistein on proliferation of cell cultures derived from human acoustic neuromas

目的 研究碱性成纤维细胞生长因子(bFGF)和酪氨酸蛋白激酶(TPK)抑制剂对培养的听神经瘤细胞增殖和DNA合成的影响作用,初步探讨其作用机制。方法 选取10例手术切除的新鲜听神经瘤组织若干,常规细胞培养,细胞种植于含10％胎牛血清的培养基中,早期传代细胞用于下一步试验。通过细胞计数和3H-TdR摄取率测定观察bFGF及TPK抑制剂genestein对听神经瘤细胞增殖及DNA合成的影响。结果 在无血清培养条件下,所测10例标本中应用bFGF有9例(9/10)测得的活细胞数和3H-TdR摄取率较对照组显著增加(P<0.05)。genistein在4例标本中对瘤细胞增殖和DNA合成均产生明显抑制效应(P<0.01),亦可阻抑bFGF的促增殖作用(P<0.01)。结论bFGF可能以自或旁分泌形式参与听神经瘤细胞增殖的调节。TPK抑制剂在体外能有效抑制听神经瘤细胞增殖,至少部分是通过抑制bFGF受体功能来实现的。

Objective To investigate the effects and possible mechanism of basic fibroblast growth factor (bFGF) and tyrosine protein kinase (TPK) inhibitor on proliferation and DNA synthesis of acoustic neuroma (AN) cells in vitro. Methods Freshly resected AN that obtained from 10 cases were placed into cell cultures. Cells from early-passage were used for the following experiments. The effects of bFGF and genistein (TPK inhibitor) on proliferation and DNA synthesis of AN cells were evaluated. Results In the conditional medium system,bFGF stimulated cell proliferation and DNA synthesis in a dose-dependent manner. The number of cells and 3H-TdR incorporation by bFGF induced in 9(9/10) cases significantly increased respectively, as compared with the control (P <0.05).In 4 cases >enistein significantly inhibited the growth of AN cells in culture (P <0. 01), and in 2 cases, bFGF-induced cell proliferation was completely inversed. Conclusion This suggested that bFGF could be involved in the modulation of AN cellular proliferation in an autocrine or paracrine manner, which possible mechanism is related to TPK receptors. Genistein-TPK inhibitor potently inhibits proliferation of AN cells in vitro,at least partially by interacting with bFGF receptor.