Objective To investigate the inhibitory effects of oridonin combined with gemcitabine on pancreatic cancer SW1990 cells in vitro, and the potential mechanisms thereof. Methods The pancreatic cancer SW1990 cells were treated with vehicle alone and various concentrations (10,20,40,80 and160μmol/L) of oridonin, followed by 24, 48 and 72 h cell culture. Effects of oridonin on cell proliferation were determined by using a CCK-8 kit. SW1990 cells were treated with oridonin (40μmol/L) and gemcitabine (20μmol/L) alone or together for 48 h, and the untreated cells were used as the con-trol. The cell survival rate was detected by CCK-8 assay. Apoptosis induction was assessed by using Annexin V-FITC kit. Semi-quantitative RT-PCR was used to examine the changes of NF-κB mRNA and XIAP mRNA expressions. Results Oridonin inhibited the growth of pancreatic cancer SW1990 cells in a dose-and time-dependent manner. Compared with the other groups, the cell survival rate was significantly lower in the combination group (P<0.05). Oridonin combined with gemcitabine induced a higher percentage of apoptosis in pancreatic cancer cells than that of oridonin or gemcitabine alone (P<0.05). Moreover, the expressions of NF-κB and XIAP mRNA in pancreatic carcinoma cells were obviously down-regu-lated in combination group (P<0.05). Conclusion Oridonin can enhance the antitumor effect of gemcitabine on pancreatic cancer in vitro, which may be related to through the down-regulation of NF-κB and its downstream of XIAP, and then induc-ing cell apoptosis in pancreatic cancer.

OBJECTIVETo evaluate the enhanced effect of gemcitabine by emodin and the possible mechanisms of the enhancement.

METHODBased on the model of SW1990 cell xenograft on athymic mouse, the mice were randomized to four groups with intraperitoneal (IP) injections of different drugs: group N (injecting 0.9% sodium chloride), group E (emodin, 40 mg x kg(-1)), group G (gemcitabine, 125 mg x kg(-1)), and group E + G (emodin 40 mg x kg(-1) and gemcitabine 80 mg x kg(-1) in combination). The tumor volume, tumor weight and body weight of mice were measured during the drug therapy. The mice were sacrificed one week after last injection of drug. Tunel assay were used used to detect the apoptosis of tumor cells. And immunohistochemistry (IHC) and Western blot (WB) were used to detect the variance of the apoptosis relative protein expression of Bax, Bcl-2, and Cytochrome C .

RESULTOne week after the last administration, the mean tumor volume and tumor weight in group E + G were significantly decreased compared to the other groups. Tunel assay showed group E + G presented apparently more apoptosis than the other groups. Immunohistochemistry (IHC) and Western blot (WB) analysis showed the expression of Cytochrome C in cytoplasmin and Bax in group E + G was apparently upregulated while the expression of Bcl-2 was apparently downregulated compared to the other groups. As a result, Bcl-2/Bax ratio was significantly decreased in group E + G.

CONCLUSIONEmodin can significantly improve the antitumor effect of gemcitabine on transplanted tumor of SW1990 cell line through apparently enhancing the tumor cell apoptosis by gemcitabine. Downregulation of Bcl-2/Bax ratio and promoting release of Cytochrome C from mitochondria is possibly one of the mechanisms of the augmented apoptosis.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Cytochromes c ; metabolism ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Drug Synergism ; Emodin ; pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Mice ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays ; bcl-2-Associated X Protein ; metabolism