17-Allylamino-17-demethoxygeldanamycin Enhances Apoptosis Induced by Oxaliplatin via Suppression of Erk Signaling Pathway in RKO Colon Cancer Cell Line

Objective To determine whether there was a synergistic effect between the Hsp90 inhibitor 17-AAG and oxaliplatin and to further investigate the roles of PI3K/Akt and Erk in apoptosis induced with 17-AAG and oxaliplatin treatment in a human colon cancer cell line. Methods Colorimetric 3-4, 5-dimethy thiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay was used to study the inhibitory effect on proliferation of RKO cell treated with 17-AAG and oxaliplatin，Apoptosis was evaluated by flow cytometry；Western blot was carried out to determine protein expression levels. Results 17-AAG could definitely inhibit the of RKO cells. When the RKO cells were exposed to 17-AAG combined with oxaliplatin for 24 h, G₂/M ratio and apoptosis rates were significantly increased. Oxaliplatin significantly decreased the protein expression of p-Akt and p-Erk. Oxaliplatin was also found to significantly increase the protein expression of Bax and Caspase-3 and to decrease the expression of Bcl-2. All these effects were enhanced when identical experiments were carried out in the presence of 17-AAG, but it had no apparent effects on the PI3K/Akt signaling pathway. Conclusion 17-AAG enhances apoptosis induced by oxaliplatin in RKO cells and there maybe exist a synergistic effect between 17-AAG and oxaliplatin. The increased expression of Bax, the decreased expression of Bcl-2 and the inhibition of Erk signaling pathway may be the underlying mechanisms leading to apoptosis.