Objective To investigate the increased cytotoxicity induced by luteolin and cisplatin cotreatment and validate its mechanism.Methods HepG2 cells were pretreated with luteolin for 1 hour or remained untreated and followed by exposure to cisplatin.Cells were stained with Hoechst,and Caspase-3 activity was detected by spectrophotometry.Cell death was detected by LDH release assay.Phosphated C-jun N-terminal kinase (JNK) and total JNK1 were detected by Western blot.Results Luteolin significantly enhanced Caspase-3 activity and HepG2 cells apoptosis by cisplatin.The cell death rates by co-treatment with different concentration of luteolin (0-20 μmol/L) and cisplatin (10 μg/ml) were much higher than cisplatin or luteolin alone treatment.Combined treatment of luteolin (20 μmol/L) with cisplatin (10 μg/ml) killed 47.66 ％ of HepG2 cells.There were significant differences on cell death between combination group and single reagent group (F =535.48,P ＜ 0.01).Combination group showed better efficacy than single reagent group.The Caspase-3 activity of HepG2 cells treated by luteolin (20 μmol/L),cisplatin (10 μg/ml) or luteolin (20 μmol/L)plus cisplatin (10 μg/ml) were 1.94,1.74 and 8.12 times of negative control group respectively.Combination treatment induced sustained activation of JNK signaling pathway.Conclusions Enhancing cisplatin-induced JNK activation by luteolin leads to increased cytotoxicity in HepG2 cells.The combination of luteolin and cisplatin is an effect apporch for improving the anticancer value of cisplatin,which has implications in cancer prevention and therapy.

Severe acute pancreatitis (SAP) is accompanied with complex pathogenic course and high mortality. The imbalance of immune response is an important cause which leads the SAP patients to the severe situation and even death. The immunomodulatory therapy can regulate the imbalance of inflammation, alleviate SAP-associated organ injury, and improve the prognosis of patients. Previous immunomodulatory therapy had some problems, such as single-object and simple-method. In recent years, some new methods of immunomodulatory therapy, such as regulating the apoptosis and mature of immune cells, applying of mesenchymal stem cells (MSCs) and multi-regulation methods, provide some new ideas and hopes for SAP therapy. This paper reviewed the history and recent research progresses of SAP immunomodulatory therapy.