HSP70 Inhibitor,VER155008,Suppresses Pheochromocytoma Cell And Xenograft Growth Via Inhibition Of PI3K/AKT/m TOR And MEK/ERK Pathways

According to the most recent World Health Organization classification,all pheochromocytomas have metastatic potential.To make matters worse,up until now there has been an absence of effective therapeutic methods to inhibit tumor growth and metastasis,especially at the occurrence of metastatic foci.Therefore,the discovery of new and effective drugs is urgently needed to improve the present situation.Because overexpression of HSP70 frequently occurs in a variety of tumor tissues,VER155008,a new inhibitor targeting HSP70,has shown an anti-tumor effect through inhibition of PI3K/AKT/m TOR and MEK/ERK pathways,both of which are closely connected with pheochromocytoma proliferation,migration and biological behaviors.In our research,we revealed that VER155008 could reduce proliferation of the pheochromocytoma cell line PC12 and induce apoptosis at a relatively low dose.Most importantly,VER155008 could effectively suppress cell migration and invasion.Subsequently,drug-effect mechanisms of VER155008 were further detected by western blot analysis,and we found that VER155008 exhibited an anti-tumor effect via down-regulating phosphorylation of the PI3K/AKT/m TOR and MEK/ERK signaling pathways.Finally,the above phenomena were further confirmed in a mice model in vivo,and the results showed that the drug significantly inhibited the xenograft tumor growth.In summary,VER155008 is a potential and promising effective drug for treating patients with pheochromocytoma,and furthermore,it could delay/inhibit tumor metastasis.