Because an inhibition of SphK1 was observed during short-term androgen deprivation in vitro (Fig. 1D) and in vivo (Fig. 2B), we verified whether transfection of LNCaP cells with SphK1 might render these cells more resistant to androgen depletion.
Since VP-16 targets S phase cells [ 27] and here we confirmed that the inhibition of BAPTA-AM dramatically increased the percentage of S phase cells, we proposed that GRP78 might render the cells sensitive to VP-16-induced apoptosis through altering the cell cycle distribution in NCI-H446 celineine.
We next tested whether pre-treatment of MM cells with the DNA demethylating agent 5-aza-cytidine (Aza, 500 nM) might render MM cells more permissive for inducing a more long-lasting growth suppression after Bz treatment.
Accordingly, expression of B7 on tumor cells induced tumor rejection in a murine model, suggesting that providing extra costimulation molecules might render tumor cells capable of effective antigen presentation, leading to their eradication in vivo.
One caveat is, the results of some trials may not be exciting, as the cytostatic effects of molecule-targeted agents might render tumor cells insensitive to cycle-active chemotherapy.
Above clinical data suggested that the skeletal microenvironment might render CaP cells resistant to castration.
Furthermore, co-culturing of the CAFs with 22Rv1 leads to the downregulation of total Bad protein levels as well as the induction of Bcl-xL protein, which in turn might render 22Rv1 cells more resistant to sorafenib.
Similar ideas have been advanced in other neurodegenerative conditions; for example, in Huntington's disease, the high frequency of synaptic activation required to maintain medium-sized spiny neurons in an excitable state might render these cells more susceptible to cellular stress (Milnerwood and Raymond, 2010).
Thus, low expression of these mitotic checkpoint regulators in advanced HCV might reflect loss of mitotic checkpoint control that could render cells to chromosomal instability.
Constitutive activation of PI3K/Akt/mTOR signaling might make cancer cells more sensitive to mTOR blockade because it would render cells more dependent on the pathway for growth.
