小檗碱联合人参皂苷Rg3对鼻咽癌裸鼠移植瘤细胞的干预作用

The Effect of Berberine Combined with Ginsenoside Rg3 on Xenograft Model of Nasopharyngeal Carcinoma

目的探讨小檗碱与人参皂苷Rg3联合使用对鼻咽癌移植瘤的干预效应及可能机制。方法建立鼻咽癌裸鼠移植瘤模型,观察小檗碱、人参皂苷Rg3单独或联合使用在体内的抑瘤效应;Tunel染色检测药物对体内肿瘤细胞凋亡的影响。Western blot、免疫组化检测小檗碱、人参皂苷Rg3单独或联合使用对体内细胞生存、增殖、凋亡相关蛋白及PI3K/AKT和MAPK/ERK信号通路关键蛋白表达的影响。结果相较于对照组,小檗碱组、人参皂苷Rg3组、顺铂组以及联合用药组移植瘤重量明显下降,细胞凋亡率增加,且联合用药组效果优于两单药组。与单独用药组相比,联合用药组移植瘤组织的生存素survivin、增殖细胞核抗原PCNA、抗凋亡蛋白Bcl-2、p-AKT及p-ERK的表达均下调,促凋亡蛋白Bax表达上调(P<0.05)。结论小檗碱、人参皂苷Rg3可协同抑制体内鼻咽癌CNE2移植瘤的生长,诱导移植瘤组织细胞的凋亡,其机制与PI3K/AKT和MAPK/ERK信号通路相关。

OBJECTIVE To study the effect and possible mechanism of berberine combined with ginsenoside Rg3 on transplanted tumor of nasopharyngeal carcinoma. METHODS The antitumor effect of berberine or/and ginsenoside Rg3 were observed after establishing xenograft model of nasopharyngeal carcinoma. The effect of drugs on the apoptosis of tumor cells in vivo was examined by Tunel staining. Western blot and immunohistochemistry were used to examine the effects of berberine or/and ginsenoside Rg3 on the expressions of cell proliferation-, apoptosis-related proteins and key proteins of PI3 K/AKT and MAPK/ERK in vivo. RESULTS Compared with the solvent control group, the weight of transplanted tumor in Berberine group, Ginsenoside Rg3 group, cisplatin group and combination group decreased significantly, while the apoptotic index was increased, and the effect of combined treatment group was better than that of two single drug groups. Compared with single drug group, the expressions of Survivin, PCNA,Bcl-2, p-AKT and p-ERK were down-regulated, while the expressions of Bax was up-regulated in the combined group(P<0.05). CONCLUSION Either single or combined use of berberine and ginsenoside Rg3 can synergistically inhibit the proliferation and induce cell apoptosis of NPC CNE2 cells in vivo. The mechanism is related to PI3 K/Akt and MAPK/ERK signaling pathways.