Abstract
背景与目的以顺铂为基础的化疗方案是晚期非小细胞肺癌的一线化疗方案,但是由于顺铂的不良反应严重及耐药性的产生均限制了它的临床应用,本研究采用联合用药的方式观察黄连素对顺铂抗肿瘤作用的影响,并探讨其可能机制。方法分别观察黄连素对肺腺癌细胞A549细胞中总Cx43蛋白、细胞膜Cx43蛋白的表达以及细胞缝隙连接功能的改变,通过标准细胞集落克隆实验观察黄连素对顺铂细胞毒性的影响;并观察PKC激酶的表达。结果黄连素在0 μM-10 μM浓度范围内对细胞无毒性,通过增加细胞内总Cx43蛋白和胞膜Cx43蛋白的表达而增强细胞缝隙连接功能;这种作用与PKC的活性被抑制相关,抑制PKC活性可以进一步增加顺铂对A549细胞的毒性作用。结论黄连素可通过增加A549细胞的缝隙连接功能而明显增强顺铂的细胞毒性。
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