ABSTRACT
Hyperadrenocorticism (HAC) often leads to vacuolar hepatopathy. The impact of trilostane treatment on serum total bile acids (SBAs) concentrations in dogs with HAC remains unknown. This study investigated SBAs concentrations in healthy dogs and those with HAC following trilostane therapy. Ten healthy dogs and fifteen dogs with HAC were prospectively enrolled. A biochemistry profile and pre- and post-prandial SBAs concentrations were determined in each dog. Dogs with HAC were reassessed at 1 and 3 months after the initiation of trilostane treatment. Dogs with HAC had significantly higher serum ALT, ALP, and GGT activities, and cholesterol, triglyceride, and pre-prandial SBAs concentrations compared to healthy dogs. After 3 months of trilostane treatment, polyuria/polydipsia and polyphagia were completely resolved in 42.8% and 35.7%, respectively. Significant improvements in serum ALT and ALP activities and cholesterol concentrations were observed within 1-3 months of trilostane treatment. However, pre- and post-prandial SBAs concentrations did not significantly decrease. These findings suggest that treatment with low-dose trilostane for 3 months appears to reduce serum liver enzyme activities, but not SBAs concentrations. Further investigation is warranted to explore the effects of low-dose trilostane treatment on SBAs concentrations for a longer duration or after achieving appropriate post-ACTH cortisol levels.
ABSTRACT
BACKGROUND: The anti-cancer effects of Gynura procumbens leaves extract (GPE) have been reported in various human cancers. However, the anti-cancer effects and molecular mechanisms of this extract on canine mammary cancer (CMC) have not yet been elucidated. OBJECTIVES: The main goal of this study was to investigate the anti-cancer properties of GPE against two CMC cell lines (CHMp-13a and CHMp-5b). METHODS: The GP leaves were extracted with 80% ethanol. Anti-cancer potentials of GPE on CHMp-13a and CHMp-5b cancer cell lines using dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT), wound healing, transwell migration, and caspase 3/7 activity assays were evaluated. The mRNA expression levels of two oncogenes: epidermal growth factor receptor (EGFR) and twist family bHLH transcription factor 1 (TWIST) and one tumour suppressor gene: phosphatase and tensin homolog (PTEN) in these cell lines were determined by quantitative real-time PCR (qRT-PCR). In addition, The EGFR and PTEN protein levels as well as protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation levels expression were also evaluated by western blot analysis. RESULTS: The results showed that GPE caused a significant concentration- and time-dependent reduction in cell proliferation of both CHMp-13a and CHMp-5b cells, detected by MTT assays. This extract also significantly suppressed cancer cell migration in both cell lines, tested by wound healing and transwell migration assays. Additionally, the increase in caspase 3/7 activity observed in both CMC cell treated with GPE suggests that GPE induced caspase 3/7 dependent apoptosis. Moreover, GPE significantly decreased EGFR mRNA and protein expression levels compared to control in both cell lines in a dose-dependent manner. CONCLUSION: These findings emphasized that GPE has an in vitro anti-cancer activity against CMC by inhibiting EGFR signalling pathway. Thus, GPE may serve as an alternative therapy in CMC with high EGFR expression.
