Our findings suggest that triptonide can efficaciously suppress PCa growth in vitro and in vivo via inhibiting the phosphorylation of mTOR and the activities of related downstream signaling pathways.
We determined whether epigenetic modulation by the histone deacetylase (HDAC) inhibitor, valproic acid (VPA), may counteract non-responsiveness to the mTOR inhibitor, temsirolimus, in prostate cancer (PCa) cells.
We evaluated the tumor tissue expression of downstream mTOR targets in patients with intermediate- and high-risk (IR/HR) PCa and their ability to predict outcome after radical prostatectomy (RP).
This study was designed to investigate whether epigenetic modulation by histone deacetylase (HDAC) inhibition might circumvent resistance towards the mechanistic target of rapamycin (mTOR) inhibitor temsirolimus in a prostate cancer cell model.
This may exploit tumor-specific characteristics, such as targeting Vascular Endothelial Growth Factor (VEGF) signaling and mammalian Target of Rapamycin (mTOR) activity in renal cancer and inducing survival factor deprivation by targeting androgen signaling in prostate cancer.
The results of the present study indicate that the non-canonical Hedgehog pathway (mTOR/S6K1/Gli1) contributes to the development and progression of prostate cancer and that Gli1 is a potential therapeutic target in the treatment of prostate cancer.
We have recently discovered a new molecular mechanism of prostate cancer docetaxel chemoresistance mediated by the mammalian target of rapamycin (mTOR)/sphingosine-kinase-1 (SK1) pathway.
Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance.
Electroporation was performed to introduce linear regulatory plasmid PrevTet-off-in and conjugative plasmid PrevTRE2-flag-E6AP into prostate cancer cell line to establish wild-type E6-AP over-expressing transgenic LNCaP cell line; Western blot assay was adopted to examine expression levels of E6-AP, mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K); PI3K inhibitor LY294002 was applied to all the cells and MTT assay was used to measure cell proliferation; Matrigel invasion chamber assay was adopted to detect cancer cell migration and invasion.
Knockdown of mTOR, Raptor or Rictor in lal(-/-) MDSCs suppressed their stimulation on proliferation of cancer cells, including B16 melanoma, Lewis lung carcinoma and transgenic mouse prostate cancer-C2 cancer cells.
In this study, we found that the expression of mLST8, a required subunit of both mTOR complex 1 (mTORC1) and complex 2 (mTORC2), was upregulated in several human colon and prostate cancer cell lines and tissues.
Tumors with concomitant PTEN deletion and activated mTOR signaling indicated by loss of p(Ser2448)-mTOR expression characterize a small (4%) but clinically significant subset of prostate cancers that might optimally benefit from anti-mTOR therapies.
Furthermore, we develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure.
Inhibition of mTOR manifested by hypophosphorylation of 4E-BP1 suggests autophagy is involved as alternative cell death mechanism. rhArg demonstrates a promising novel agent for prostate cancer treatment.
However, the oncogenic contributions downstream of the PI3K pathway made by mammalian target of rapamycin complex 1 (mTORC1)-mediated cell growth signal transduction in PCa have yet to be elucidated in detail.
In this review, we consider the rationale for pursuing mTOR as a therapeutic target in prostate cancer and summarize preclinical and clinical studies of mTOR inhibition in prostate cancer.
The mammalian target of rapamycin (mTOR) kinase is an important component of PTEN/PI3K/Akt signaling pathway, which is frequently deregulated in prostate cancer (CaP).
Inhibition of mammalian target of rapamycin (mTOR), a downstream target of phosphoinositide 3-kinase signaling, results in cell cycle arrest and apoptosis in multiple in vitro and in vivo models of prostate cancer.
Moreover, conditioned medium from PC3 PDGF-D cells significantly increased the tube formation of human umbilical vein endothelial cells, which was inhibited by B-DIM treatment concomitant with reduced full-length and active form of PDGF-D. Our results suggest that B-DIM could serve as a novel and efficient chemopreventive and/or therapeutic agent by inactivation of both mTOR and Akt activity in PDGF-D-overexpressing prostate cancer.