Objective
To observe the antitumor effect of 131I-17-allylamino-17-demethoxygeldanamycin (131I-17-AAG) in vitro/in vivo and explore its antitumor mechanism with a view to its potential therapeutic application.
Methods
131I-17-AAG was prepared by the reaction of 17-AAG with Na [131I] in the presence of hydrogen peroxide. The effects of 13117-AAG on cell growth inhibition and cell cycle distribution in vitro were studied in BEL-7402 cells lines. Following BEL-7402 tumor implantation by subcutaneous xenografts into nude mice, the reagents were injected through the tail vein, and the tumor volume was measured and analyzed. At the end of the experiment, tumor specimens were processed for histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis. The expression change of Akt2 was tested by Western-blot analysis.
Results
Methyl-thiazolyl-tetrazolium assay showed inhibition rates of 27.7 ± 5.3%, 57.3 ± 4.3%, and 63.7 ± 3.1%, in Na131I group, 17-AAG group, and 131I-17-AAG group, respectively. The inhibition rate in the 131I-17-AAG group differed significantly between Na131I group and 17-AAG group (F = 229.49, P < 0.001). Following 48 h of treatment with the drug in each group, flow cytometry analysis indicated that detected sub-G peaks (black) were 1.54 ± 0.13%, 5.72 ± 1.05%, 12.97 ± 1.44%, and 20.65 ± 1.36%, in dimethyl sulfoxide (DMSO) group, Na131I group, 17-AAG group, and 131I-17-AAG group, respectively. Following infusion for 32 days, the tumor volumes in the 131I-17-AAG group were significantly smaller than those in the DMSO group (F = 24.18, P < 0.001) or the 131I group (F = 20.68, P < 0.001). Histopathological and TUNEL analyses showed that 131I-17-AAG inhibited the proliferation of tumor cells and induced apoptosis. The expression of Akt2 in 131I-17-AAG was significantly lower than that in the DMSO group or 131I group.
Conclusions
131I-17-AAG can effectively inhibit the growth of BEL-7402 tumor cells in vitro and in vivo. 131I-17-AAG is a promising agent for the treatment of BEL-7402 cell tumor.