蛋白激酶C在结肠癌多细胞耐药中的实验研究

目的：探讨蛋白激酶C（protein kinase C,PKC）在结肠癌细胞多细胞耐药中的作用。方法：采用体外三维细胞培养的方法,通过应用不同剂量PKC抑制剂Staurosporine（SP）对三维（3D）培养结肠癌HT-29细胞药物敏感性、核因子-κB（NF-κB）活性及PKC活性的影响的研究,探讨PKC在结肠癌细胞群集耐药中的作用。结果：3D培养结肠癌细胞中PKC、NF-κB活性较二维（2D）培养细胞明显增高,氟尿嘧啶（5-FU）的药物敏感性降低;SP不同浓度处理HT-29球形细胞可抑制其PKC及NF-κB活性,对5-FU的药物敏感性增加,在一定浓度范围内,随着SP浓度的增加,抑制作用逐渐增强,存在量效关系。结论：PKC在结肠癌细胞群集耐药中有一定作用,抑制PKC活性,可增加结肠癌球形细胞对5-FU的敏感性。

The experimental study of PKC on multicellular resistance(MCR) of colorectal carcinoma HT-29 cells

Objective：To study the effects of protein kinase C（PKC）on multicellular resistance（MCR）of colorectal carcinoma HT-29 cells in vitro.Methods：HT-29 cells were cultured as three-dimensional model using liquid overlay technique or as monolayer using routine method.It was studied that the activities of PKC and NF-κB and the sensitivity to 5-FU in HT-29 spheroids by the PKC inhibitor Staurosporine（SP）treatment in different concentrations.Results：The activities of PKC and NF-κB in HT-29 spheroids were higher than that of monolayer.SP treatment in different concentrations not only could inhibit the activities of PKC and NF-κB but also could induce the sensitivity to 5-FU in HT-29 spheroids.The larger the dosage was used,the more intensifide inhibitive effct could be obtained.Conclusion：There are regulating mechanisms on multicellular resistance of colorectal carcinoma HT-29 cells by PKC in vitro,the inhibition of PKC could induce sensitivity to 5-FU in HT-29 spheroids.