Spiclomazine displays a preferential anti-tumor activity in mutant KRas-driven pancreatic cancer.

ABSTRACT: Ras-targeted therapy represents a 'holy grail' in oncology. Based on our model prediction, Spiclomazine freezing the intermediate conformation of activated Ras is central to cancer therapeutics. We show here that Spiclomazine leads to an effective suppression in Ras-mediated signaling through abrogating the KRas-GTP level in the KRas-driven pancreatic cancer. The Ras-mediated signaling inhibition leads to dramatically reduced survivals of five KRas-driven pancreatic cancer cell lines with IC₅₀ ranging 19.7~74.2 μM after 48 hours of treatment. However, no significant changes have been observed for normal cell lines. It is worth mentioning that the mutant KRas-driven cancer cells are more sensitive towards Spiclomazine than the wild-type KRas cancer cel

SUBMITTER: Guo X 

PROVIDER: S-EPMC5805527 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature