格尔德霉素对胆囊癌的体外治疗作用

目的 观察格尔德霉素(GA)对胆囊癌细胞生长、运动和侵袭的影响及其化疗增敏作用.方法 噻唑蓝(MTT)比色法检测(0、0.0064、0.032、0.16、0.8、4、20、100)×10-6 mol/L浓度梯度的GA对胆囊癌细胞GBC-SD生长影响;观察1 μmoL/L的GA对0.1倍最大血药浓度(Maximal plasma concentration,Cmax)的5-氟尿嘧啶(5-Fu,Cmax 10 mg/L)、丝裂霉素(MMC,Cmax 3 mg/L)、阿霉素(ADM,Cmax 0.4 mg/L)的化疗增敏作用.应用迁移运动及侵袭实验观察1μmol/L的GA体外对胆囊癌细胞运动、侵袭能力的影响.结果 GA体外对胆囊癌细胞有较强的抑制作用,半数抑制浓度(Inhibitory concentration 50%,IC50)在20μmol/L水平.1μmol/L低生长抑制浓度的GA能够增加传统化疗药物对GBC-SD生长的抑制作用,有明显的增效作用;同时低浓度的GA可以抑制肝细胞生长因子(HGF)对GBC-SD运动迁移和侵袭能力的诱导作用.结论 GA有可能成为胆囊癌化疗和抗转移的有效药物.

Effects of Geldanamycin on gallbladder carcinoma in vitro

Objective To study the effects of Geldanamycin (GA) on the proliferation, motility and invasion of gallbladder carcinoma (GBC) cells and its synergistic effects with S-Fu, ADM and MMC in vitro. Methods Methyl thiazolyl tetrazolium(MTT) assays were used to investigate the effects of GA (0,0.0064,0.032,0.16,0.8,4,20, 100)×10-6 mol/L] on the proliferation of GBC-SD. The enhanced antitumor activities of 5-Fu (Cmax 10 mg/L) , MMC (Cmax 3 mg/L) and ADM (Cmax 0.4 mg/L) at 0.1 × Cmax were observed in combination with GA at 1 μmol/L (a very low cytotoxic concentration). Motility and invasion abilities were tested to evaluate the inhibitory effects of GA at 1 μmol/L. Results In MTT assays, GA could inhibit growth of cancer cells sharply at the concentration of 20 μmol/L (IC50). Although it couldn't postpone the motility and invasion apparently by itself, GA at 1 μmol/L could inhibit the HGF/SF-mediated increase of motility and invasion. The enhanced antitumor activity of 5-Fu, MMC and ADM was observed in combination with GA at 1 μmol/L The synergistic effects were very significant. Conclusion GA may be potent agents to inhibit development and metastasis of GBC in the near future.