An experimental study on the antitumor effect of 131I-17-AAG in vitro and in vivo

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 N^a131I 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.