BackgroundThe malignant osteoblastoma has poor prognosis, thus the search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects both in vivo and in vitro, however, its role in osteoblastoma is still not clear. Key FindingsSalinomycin induced both apoptosis and autophagy in cultured U2OS and MG-63 osteoblastoma cells. Inhibition of autophagy by 3-methyladenine (3-MA), or by RNA interference (RNAi) of light chain 3B (LC3B), enhanced salinomycin-induced cytotoxicity and apoptosis. Salinomycin induced a profound AMP-activated protein kinase (AMPK) activation, which was required for autophagy induction. AMPK inhibition by compound C, or by AMPKα RNAi prevented salinomycin-induced autophagy activation, while facilitating cancer cell death and apoptosis. On the other hand, the AMPK agonist AICAR promoted autophagy activation in U2OS cells. Salinomycin-induced AMPK activation was dependent on reactive oxygen species (ROS) production in osteoblastoma cells. Antioxidant n-acetyl cysteine (NAC) significantly inhibited salinomycin-induced AMPK activation and autophagy induction. ConclusionsSalinomycin activates AMPK-dependent autophagy in osteoblastoma cells, which serves as a negative regulator against cell apoptosis. AMPK-autophagy inhibition might be a novel strategy to sensitize salinomycin’s effect in cancer cells.

Osteopontin (OPN) has been implicated in tumor development and progression over the last few years. However, the prognostic value of OPN overexpression in patients with breast cancer remains controversial. We performed a meta-analysis to investigate the association of OPN expression in the tumor with the clinicopathological characteristics and survival of breast cancer patients. A total of 8 studies met the inclusion criteria and were entered in the meta-analysis. The data analysis demonstrated that OPN expression was positively associated with lymph node metastasis [pooled odds ratio = 2.026, 95% confidence interval (CI): 1.199-3.425, P=0.008, random-effects model]. We also found that OPN expression was positively associated with overall survival [hazard ratio (HR) = 3. 69, 95% CI: 1. 45-9.42, P=0.000, random-effects model) and disease -free survival (pooled HR=2.40, 95% CI: 1.27-4.55, P=0.007, fix ed -effects model). Based on the results of this study, we concluded that OPN overexpression in the tumor is a candidate positive prognostic biomarker for breast cancer patients.