In contrast, lower inhibitor U0126 AMPK B1 expression may reduce the number of AMPK heterotri meric complexes, which leads to lower AMPK activity in advanced ovarian cancers. A previous study has dem onstrated that knockouts of AMPK B1 and B2 led to reduced AMPK activity in most tissues and significant reductions in bone mass in mice. Additionally, the post translational modification of AMPK B1, that is, myristoylation and phosphorylation, could affect AMPK activity. Based on these findings, we believe that re duced expression of AMPK B1 diminishes the amount of AMPK heterotrimeric complexes and their activity in aggressive, advanced ovarian cancer cells. Our findings on the negative regulation of the AKT pathway by AMPK B1 is in line with those reported by Feng et al.

AMPK B1 has been found to be a stress responsive gene that can be induced in a p53 dependent or p53 independent manner . therefore, induction of AMPK B1 expression could negatively regulate the IGF 1 Inhibitors,Modulators,Libraries AKT mTOR pathways. The ability to simultaneously upregulate AMPK activity and down regulate AKT signal ing leads to cell growth inhibition. Moreover, AMPK B1 overexpression could inhibit ovarian cancer cell migration and invasion, and this effect is most likely mediated through the down regulation of the JNK pathway. We have previously demonstrated that down regulation of the JNK pathway using a JNK inhibitor significantly inhibited cell motility. Similarly, inhibition of the AKT and ERK pathways Inhibitors,Modulators,Libraries using their respective inhibitors, wort mannin and U0126, could reduce cell proliferation rates, which indicates the importance of AMPK B1 ex pression in controlling cell proliferation, migration, and invasion.

Indeed, AMPK B1 expression correlates well with clinicopathologic data, which show that early stage tumors have high levels of AMPK B1, whereas advanced stage, high grade or metastatic ovarian cancers have lower AMPK B1 levels. In conclusion, Inhibitors,Modulators,Libraries our findings suggest that the expression level of AMPK B1 is able to determine the amount of AMPK heterotrimeric complexes and, hence, the activity level of AMPK in advanced ovarian cancer cells. Downreg ulation of AMPK B1 seems to be another mechanism that leads to lower AMPK activity in advanced ovarian cancer cells. Inhibitors,Modulators,Libraries Based on the data showing that enforced expression of AMPK B1 elevates AMPK activity but decreases AKT, ERK and JNK activities as well as abrogates Inhibitors,Modulators,Libraries its oncogenic capacities in cell growth, migration, invasion and sensitizing chemoresistant ovarian cancer cells to cisplatin induced cell apoptosis, AMPK B1 may be a sellectchem potential therapeutic target in advanced ovarian cancer treatment.