Paclitaxel is one of the best anticancer agents that has been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we obtained evidence that the active mutant IPP5 (8-60hIPP5m), the latest member of the inhibitory molecules for protein phosphatase 1, sensitizes human cervix carcinoma cells HeLa more efficiently to the therapeutic effects of paclitaxel. The combination of 8-60hIPP5m with paclitaxel augmented anticancer effects as compared to paclitaxel alone as evidenced by reduced DNA synthesis and increased cytotoxicity in HeLa cells. Furthermore, our results revealed that 8-60hIPP5m enhances paclitaxel- induced G2/M arrest and apoptosis, and augments paclitaxel-induced activation of caspases and release of cytochrome C. Evaluation of signaling pathways indicated that this synergism was in part related to down- regulation of NF-?B activation and serine/threonine kinase Akt pathways. We noted that 8-60hIPP5m down- regulated the paclitaxel-induced NF-?B activation, I?Bα degradation, PI3-K activity and phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-?B. Together, our observations indicate that paclitaxel in combination with 8-60hIPP5m may provide a therapeutic advantage for the treatment of human cervical carcinoma.