Recurrences of hormone-refractory prostate cancer highly affect the therapeutic outcome. Although anti-androgen therapy prolongs survival in prostate cancer patients, resistance rapidly develops and is often associated with increased androgen receptor expression and upregulated HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually failed due to the reciprocal feedback loop. Here, we demonstrated that herbal extract of Wedelia chinensis (WCE) effectively disrupted the androgen receptor, HER2/3, and AKT signaling network and therefore enhanced therapeutic efficacy of androgen ablation in PCa. Overall design: To further study WCE effect, 22Rv1 prostate cancer cells were treated by vehicle control or 10 μg/mL of WCE for 16 hr. Total RNA expressions were analyzed in cDNA microarray.