The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1). The effect on proliferation, radiosensitivity, apoptosis, cell cycle distribution, reactive oxygen species production, DNA repair, gene and protein expression was investigated. Furthermore, this treatment combination was also assessed in vivo. Metformin was shown to interact with Hh signaling by inhibiting the effector protein glioma-associated oncogene homolog 1 (GLI1) in PCa cells both in vitro and in vivo. The combination of metformin and GANT61 significantly inhibited PCa cell growth in vitro and enhanced the radiation response of 22Rv1 cells compared to either single agent. Nevertheless, neither the growth inhibitory effect nor the radiosensitization effect of the combination treatment observed in vitro was seen in vivo. Although the interaction between metformin and Hh signaling seems to be promising from a therapeutic point of view in vitro, more research is needed when implementing this combination strategy in vivo.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lBuYlt
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Use of communication coaching that included a question prompt list —or structured lists of questions given to patients prior to consultation...
-
Abstract BACE1 is an indispensable enzyme for generating β-amyloid peptides, which are excessively accumulated in brains of Alzheimer'...
-
Rhinoplasty is perhaps the most challenging and elegant procedure within all of plastic surgery. In this issue of JAMA Facial Plastic Surger...
-
This Viewpoint discusses variances in cardiovascular prevention guidelines from the United States, Europe, and Canada and the debate surroun...
-
Symptom Presentation and Prescription of Sleep Medications for Veterans With Posttraumatic Stress Disorder. J Nerv Ment Dis. 2017 Jan ...
-
Objectives Oral health inequality in children is a widespread and well-documented problem in oral healthcare. However, objective and reliabl...
-
International Journal of Environmental Research... Latest Results for Sleep and BreathingIntermitt... Evolutionary Biology News -- S...
-
Abstract Endurance exercise generates CO 2 via aerobic metabolism; however, its role remains unclear. Exogenous CO 2 by transcutaneous d...
-
Regulatory T cells (Treg) represent a minor sub-population of T lymphocytes which is crucial for the maintenance of immune homeostasis. Here...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου