Abstract
BACKGROUND AND OBJECTIVE: Cisplatin is a standard first-line chemotherapeutic agents for treating advanced non-small cell lung cancer. Unfortunately, the clinical application cisplatin is restricted because it induces serious adverse reaction. The aim of this study is to investigate the influence and probable mechanism of berberine on cisplatin antineoplastic effect on lung cancer A549 cells. METHODS: The total Cx43 protein amount, localization of Cx43 on cell membrane, and gap junction function were observed after the A549 cells were treated with berberine. The influence 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. The gap junction function between the cells was enhanced through increased Cx43 protein expression and localization of Cx43 on the membrane after berberine treatment. The 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. This effect was associated with the PKC activity. The cisplatin-induced inhibition of colony growth was enhanced when berberine was combined with cisplatin. CONCLUSIONS: Berberine can obviously increase the antitumor effect of cisplatin by enhancing the function of the gap junction possibly in A549 cells.
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