格尔德霉素对胆囊癌的体外治疗作用

Effects of Geldanamycin on gallbladder carcinoma in vitro

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.

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.