Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth
Abstract
Abnormal activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been demonstrated in certain types of cancer, including cholangiocarcinoma (CCA). This pathway may therefore be a promising target for CCA treatment. The present study assessed the inhibitory effect of NVP-BKM120, a pan-class I PI3K inhibitor, on CCA cell growth. This inhibitory effect was determined using CCA cell lines and in CCA-inoculated mice. The result from sulforhodamine B (SRB) assay demonstrated that NVP-BKM120 treatment inhibited CCA cell growth in a dose-dependent manner, even at the lowest tested concentration. The in vivo study revealed that oral administration of NVP-BKM120 (10 or 30 mg/kg) to CCA-inoculated nude mice led to a reduction in tumor growth when compared with controls, which was indicated by an immunohistochemical assay for Ki67 expression. In addition, the result from TUNEL assay demonstrated that NVP-BKM120 induced cancer cell death without any signs of toxicity, which indicated by the body weight of mice (data not shown). Western blot analysis demonstrated that NVP-BKM120 inhibited CCA cell growth by suppressing RAC serine/threonine protein kinase/mechanistic target of rapamycin activation and inhibiting the phosphorylation...Continue Reading
References
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
AKT Pathway
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.