CAJ | 학술논문

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0μM-10μM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，0.1μM、1μM、10μM黄连素可以显著增强细胞间的荧光传递，与空白对照组相比，黄连素预处理后的细胞间荧光传递功能分别增加了33.3%(P=0.002,3)、67.0%(P<0.001)、160.0%(P<0.001)，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。
배경여목적이순박위기출적화료방안시만기비소세포폐암적일선화료방안，단시유우순박적불량반응엄중급내약성적산생균한제료타적림상응용，본연구채용연합용약적방식관찰황련소대순박항종류작용적영향，병탐토기가능궤제。방법분별관찰황련소대폐선암세포A549세포중총Cx43단백、세포막Cx43단백적표체이급세포봉극련접공능적개변，통과표준세포집락극륭실험관찰황련소대순박세포독성적영향；병관찰PKC격매적표체。결과황련소재0μM-10μM농도범위내대세포무독성，통과증가세포내총Cx43단백화포막Cx43단백적표체이증강세포봉극련접공능，0.1μM、1μM、10μM황련소가이현저증강세포간적형광전체，여공백대조조상비，황련소예처리후적세포간형광전체공능분별증가료33.3%(P=0.002,3)、67.0%(P<0.001)、160.0%(P<0.001)，저충작용여PKC적활성피억제상관，억제PKC활성가이진일보증가순박대A549세포적독성작용。결론황련소가통과증가A549세포적봉극련접공능이명현증강순박적세포독성。
Background and objectiveCisplatin is a standard ifrst-line chemotherapeutic agents for treating ad-vanced non-small cell lung cancer. Unfortunately, the clinical application cisplatin is restricted because it induces serious adverse reaction. hTe aim of this study is to investigate the inlfuence and probable mechanism of berberine on cisplatin antineoplastic effect on lung cancer A549 cells.MethodshTe total Cx43 protein amount, localization of Cx43 on cell membrane, and gap junction function were observed atfer the A549 cells were treated with berberine. hTe inlfuence of berberine on the antitumor action of cisplatin was detected by standard colony-forming assay. Protein kinase C (PKC) protein, which regulates the gap junction, was subsequently determined.Results Berberine did not affect cell survival at concentrations of 0 μM to 10 μM in the A549 cells. hTe gap junction function between the cells was enhanced through increased Cx43 protein expression and localization of Cx43 on the membrane atfer berberine treatment. hTe intercellular dye coupling through gap junction increased when the cells exposed to 0.1 μM, 1 μM, 10 μM berberine [33.3% (P=0.002,3), 67.0% (P<0.001), 160.0% (P<0.001)] compared withcontrols. hTis effect was associated with the PKC activity. hTe cispla-tin-induced inhibition of colony growth was enhanced when berberine was combined with cisplatin.ConclusionBerberine can obviously increase the antitumor effect of cisplatin by enhancing the function of the gap junction possibly in A549 cells.