The cdk inhibitor roscovitine nearly com-pletely blocked TXL induced apoptosis with or without secretase inhibitors. Compared with that of the automobile treated get a grip on group, while tumor size was reduced by 800-724 in animals treated with TXL DAPT therapy with TXL alone, tumor size was reduced by 30%. No mouse died through the observation period. Weight reduction and skin problems were not seen throughout the different treatment cycles. We showed that secretase inhibitors increased anti microtubule agent induced mitotic arrest and apoptosis specifically in colon cancer cells. On the other hand, particular knockdown of cdk1 didn’t influence TXLinduced mitotic arrest and apoptosis with o-r MAPK assay without secretase inhibitors. Silencing of Notch/CBF1 signaling by RNA interference did not increase TXL induced mitotic arrest and apoptosis. Finally, we showed the combined use of TXL and secretase inhibitors might be a novel therapeutic strategy against colon cancers using a xenograft model. A previous study showed the secretase inhibitor DAPT restricted cancer growth and community formation. Interestingly, apoptosis of cancer cell lines induced by inhibitors was preceded by a G2/M growth arrest. In addition, therapy with secretase inhibitors induces apoptosis in Kaposis sarcoma cells. Nevertheless, our information showed that DAPT by itself could not prevent growth and community formation and didn’t induce apoptosis and cell cycle arrest in SW480 and DLD 1 cells. These data indicate that the results of secretase inhibitors on growth or apoptosis are cell typ-e dependent. On the other hand, DAPT once was demonstrated to potentiate TRAIL induced apoptosis in cholangiocarcinoma cells. Today’s data provide evidence, for the first time, that secretase inhibitors particularly augment mitotic arrest and apoptosis in colon cancer cells caused by anticancer drugs acting primarily within the M phase. This might be a clinically important process of resistance to taxanes because phase 2 studies showed that taxanes were ineffective against colorectal cancers. Significantly, the current data showed the 3 different secretase BI-1356 inhibitors had similar effects on TXL induced mitotic arrest and apoptosis. These data show that the increase in TXLinduced mitotic arrest and apoptosis by DAPT could be phenomena common to secretase inhibitors. In-addition, we confirmed that secretase inhibitors superior TXL induced mitotic arrest in SW480 and DLD 1 cells, which was shown by cyclin B1 protein level, MPM 2 reactivity, and elevated cyclin B1/cdk1 action. Taxane and VCR immediately work on spindle microtubules to produce mitotic arrest, which is considered to be an important element in their cytotoxic func-tion. The importance of mitotic arrest in-the induction of TXL induced apoptosis is found.