Effect of mitogen-activated protein kinase signal transduction pathway on multidrug resistance induced by vincristine in gastric cancer cell line MGC803

AIM:To investigate the correlation between mitogen-activated protein kinase (MAPK) signal transduction pathway and multidrug resistance (MDR) in MGC803 cells.METHODS:Western blot was used to analyze the expression of MDR associated gene in transient vincristine (VCR) induced MGC803 cells, which were treated with or without the specific inhibitor of MAPK, PD098059.Morphologic analysis of the cells treated by VCR with or without PD098059 was determined by Wright-Giemsa staining. The cell cycle analysis was performed by using flow cytometric assay and the drug sensitivity of MGC803 cells which were exposed to VCR with or without PD098059 was tested by using MTT assay.RESULTS:Transient exposure to VCR induced P-gp butnot MRP1 or GST-π expression in MGC803 cells and the expression of P-gp was inhibited by PD098059.Apoptotic bodies were found in the cells treated with VCR or VCR+PD098059. FCM results indicated that more MGC803 cells showed apoptotic phenotype when treated by VCR and PD098059 (rate:31.23%) than treated by VCR only (rate:18.42%) (P<0.05).The IC50(284±13.2 μg/L) of MGC803 cells pretreated with VCR was 2.24-fold as that of negative control group (127±17.6μg/L) and 1.48-fold as that of the group treated with PD098059 (191±27.9μg/L).CONCLUSION:This study shows that the expression of P-gp can be induced by transient exposure to VCR and this induction can be prevented by PD098059, which can block the activity of MAPK. MAPK signal transduction pathway may play some roles in modulating MDR1 expression in gastric cancer.

Survival trends in gastric cancer patients of Northeast China

AIM: To describe survival trends in patients in Northeast China diagnosed as gastric cancer. METHODS: A review of all inpatient and outpatient records of gastric cancer patients was conducted in the First Affiliated Hospital of China Medical University. All the gastric cancer patients who satisfied the inclusion criteria from January 1, 1980 through December 31, 2003 were included in the study. The main outcomes were based on median survival and 3-year and 5-year survival rates, by decade of diagnosis. RESULTS: From 1980 through 2003, the median survival for patients with gastric cancer (n = 1604) increased from 33 mo to 49 mo. The decade of diagnosis was not significantly associated with patient survival for gastric cancer (P = 0.084 for overall survival, and P = 0.150 for 5-year survival); however, the survival rate of the 2000s was remarkably higher than that of the 1980s (P = 0.019 for overall survival, and P = 0.027 for 5-year survival).CONCLUSION: There was no significant difference of survival among each period; however, the survival rate of the 2000s was remarkably higher than that of the 1980s.

Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide

AIM: This study was designed to examine the hypothesis that gender differences in I/R injury are associated withendothelial cell nitric oxide synthase (eNOS)-derived nitric oxide (NO).METHODS: Wistar rats were randomized into seven experimental groups (12 animals per group). Except for the sham operated groups, all rats were subjected to total liver ischemia for 40 min followed by reperfusion. All experimental groups received different treatments 45 min before the laparotomy. For each group, half of the animals (six) were used to investigate the survival; blood samples and liver tissues were obtained in the remaining six animals after 3 h of reperfusion to assess serum NO, alanine aminotransferase (ALT) and TNF-α levels, liver tissuemalondialdehyde (MDA) content, and severity of hepatic I/R injury.RESULTS: Basal serum NO levels in female sham operated (FS) group were nearly 1.5-fold of male sham operated (MS) group (66.7±11.0 μmol/L vs 45.3±10.1μmol/L, P＜0.01). Although serum NO levels decreased significantly after hepatic I/R (P＜0.01, vs sham operated groups), they were still significantly higher in female rat (F) group than in male rat (M) group (47.8±8.6 μmol/L vs 23.8±4.7 μmol/L, P＜0.01). Serum ALT and TNF-α levels, and liver tissue MDA content were significantly lower in F group than in M group (370.5±46.4 U/L, 0.99±0.11 μg/L and 0.57±0.10 μmol/g vs668.7±78.7 U/L, 1.71±0.18 μg/Land 0.86±0.11 μmol/g, respectively, P＜0.01). I/R induced significant injury to the liver both in M and F groups (P＜0.01 vs sham operated groups). But the degree of hepatocyte injury was significantly milder in F group than in M group (P＜0.05 and P＜0.01). The median survival time was six days in F group and one day in M group. The overall survival rate was significantly higher in F group than in M group (P＜0.05). When compared with male rats pretreated with saline (M group), pretreatment of male rats with 17-β- estradiol (E2) (M+E2 group) significantly increased serum NO levels and significantly decreased serum ALT and TNF-α levels, and liver tissue MDA content after I/R (P＜0.01).The degree of hepatocyte injury was significantly decreased and the overall survival rate was significantly improved in M+E2 group than in M group (P＜0.01 and P＜0.05). TheNOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) treatment could completely abolish the protective effects of estrogen in both male and female rats. CONCLUSION: The protective effects afforded to female rats subjected to hepatic I/R are associated with eNOSderived NO.

Ability of a Specific ERK Signal-Pathway Inhibitor to Reverse P-Glycoprotein- Mediated Vincristine Resistance in Colon Cancer Cell Unes

OBJECTIVE To investigate the effect of a specific inhibitor PD098059 of the extracellular-signal regulated protein kinase (ERK) pathway on the P-glycoprotein (P-gp)-mediated resistance of colon cancer cell lines SW480/VCR and CoLo205NCR.METHODS SW480NCR and CoLo205NCR cells were generated byexposuring SW480 and CoLo205 cells to vincristine (VCR) (30 ng/ml) for 72h, which resulted in a comparatively higher level of P-gp expression.Western blotting was used to analyze P-gp, MRP, LRP, GST-'rr and TOPOIIexpression after exposuring the SW480 and CoLo205 cells to VCR (30 ng/ml)for 72 hrs. P-gp and pERK1/2 expressions was analyzed in SW480NCR andCoLo205/VCR cells treated with or without the specific inhibitor of MEK,PD098059. The MTT assay was used to determine the susceptibility ofSW480NCR and CoLo205NCR cells to VCR, treated with or withoutPD098059.I^F.SULI"S The results showed that VCR induced a comparatively higher levelof P-gp expression in the cell lines, but not that of MRP, LRP, GST-n- orTOPOII. P-gp expression levels were depressed significantly in SW480/VCR and COLO205/VCR cells by the specific inhibitor of MEK, PD098059.The IC50 (248 +19.6 and 215 +10.7 ng/ml) to VCR of SW480/VCR andCoLo205/VCR cells exhibited a 2.16 and 2.03-fold higher resistancecompared to the negative control group (SW480 and CoLo205 cells)(115+15.6 and 106 +11.9 ng/ml), but a 1.35 and 1.21 -fold higher resistance thanthe group treated with VCR (30 ng/ml)+ PD098059 (184 + 21.8 and 177+19.4 ng/ml).CONCLUSION This study shows that the expression of P-gp can beinduced by exposuring cells to VCR, and that this induction can be reversedby inhibiting the ERK signaling pathway at the point of MEK by its specificinhibitor, PD098059. The ERK signal-transduction pathway may play a rolein modulating mdrl expression in colon cancer.

Synthesis and Fluorescence of alt-Copoly[1, 4-divinylenebenzene/1, 4-bis(dimethylsilylene)benzene]

Silicon inserted π conjugated copolymer was synthesized by Heck reaction with moderate molecular weight. This silicon containing copolymer is thermally stable to 400 'C, while emission of this polymer is blue-shifted compared with polyphenylenevinylene greenish emission. It shows potential application as organic emitter in OLED.