ABSTRACT
As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.
Subject(s)
Humans , Animals , Female , Rabbits , Breast Neoplasms/drug therapy , Cantharidin/pharmacology , Signal Transduction/drug effects , MAP Kinase Signaling System/drug effects , Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Drug Screening Assays, Antitumor , Cell Movement/drug effects , Cell Line, Tumor , Cell Proliferation/drug effectsABSTRACT
Objectives: To assess the impact of system factors and modifiable interventions on outcome of cardiac arrest in a pediatric intensive care unit. Design: Retrospective medical record review. Setting: Pediatric intensive care unit of a hospital in China. Participants: Children (age<14 yrs) who had cardiac arrest within our PICU over a period of two years. Results: Sixty-one of the 94 cardiac arrest events were successfully resuscitated. There was no significant association between personal and unit factors with immediate outcomes in our unit. The rate of unsuccessful resuscitation in sedated patients and those without sedation was 26% and 50%, respectively. Unsuccessful resuscitation occurred in 19% of patients who were on positive pressure ventilation as compared with 74% for those without positive pressure ventilation. Arrests which had resuscitation attempts that lasted more than 30 min had 135-fold higher odds of unsuccessful outcome. 78% of patients who received base supplement at the time of arrest had unsuccessful resuscitation compared with 21% for those without base supplement. Conclusions: Our data shows no impact of system factors on the outcome of cardio-pulmonary resuscitation in our PICU. Prearrest sedation in pediatric critical ill patients might be beneficial to the outcome of cardiac arrests.