3.7 | DSG inhibited the growth of PCa xenografts.
Epigenetic suppression of TSGs and escape of cellular senescence are two critical hallmarks of tumor progression(Hanahan&Weinberg, 2011). Therefore, development of new therapeutics by targeting these two hallmarks is therefore ideal avenue. Based on the in vitrofindings that DSG is effective in reactivating TSGs expression and triggering cell senescence, we then examined the therapeutic efficacy of DSG on the pre-existing in vivo tumor xenografts. As expected, DSG inhibited the growth of DU145 tumor xenografts in a dose-dependent manner (Fig. 7a-b-c-d). Consistent with the in vitro data, DSG increased the expression of such typical TSGs as p16 , LXNand p21 inside the tumor nodes (Fig. 7e). Compared to the control mice, we found no statistically significant change in the body weight of DSG-treated mice (Fig. 6f). Meanwhile, Histopathological examination showed DSG treatment did not induce obvious liver and kidney toxicity (Fig. 6g). DSG demonstrated strong anti-PCa efficacy in both in vitro cell lines and in vivo tumor xenografts, and the inhibitory effect is closely correlated with the protein levels of UHRF1, suggesting a high tumor specificity.