To investigate the effects of Jianpi Jiedu Formula (JPJDF), a compound Chinese herbal medicine, on vascular endothelial growth factor (VEGF) expression induced by Helicobacter pylori (Hp) in human gastric cancer cells, and to explore the possible mechanism.

Background and purpose:Cyclooxygenase-2 (Cyclooxygenase-2,COX-2) is an important rate-limiting enzyme that is responsible for transformation of arachidonic acid into prostaglandins(PGs).Although Helicobacter pylori(Hp) infection-induced gastric over-expression of COX-2 (COX-2) is an important factor of gastric cancer,the mechanism of COX-2 expression in gastric mucosa cells infected with Hp is still not clear.Our study was to reveal the effect of Hp on expression of COX-2(cyclooxygenase-2),the impact of p38MAPK signaling pathway in human gastric epithelial cancer cells line MKN45,and to investigate the potential mechanisms of expression of COX-2. Methods:The expression of COX-2 mRNA infection by standard Hp NCTC11637 in human gastric epithelial cancer cells line MKN45 was evaluated by real-time fluorogenic quantitative polymerase chain reaction (RFQ-PCR).The effect of infection by Hp on COX-2 expression,activation of p38MAPK and its downstream of the ATF-2 was assayed by Western blot.Results:The expression of COX-2 mRNA in MKN45 cells infected by Hp compared with control group,COX-2 mRNA had 3 fold,7.2 fold,5.1 fold,4.3 fold up-regulation after 3 hrs,6 hrs,9 hrs,12 hrs,respectively. COX-2 mRNA expression in each time group was significantly higher than that in the control group(P

The present study was aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet) in vitro and in vivo. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The ADM accumulation and the protein levels of P-glycoprotein (P-gp) were detected by flow cytometry. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of BrTet and Tet was investigated by using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. The results showed that BrTet at 0.25, 0.5 and 1 micromol/L reversed the resistance to ADM in MDR K562/A02 cells in a dose-dependent manner. Flow cytometry suggested that BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in K562/A02 cells, and down-regulated mdr1 expression. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, intraperitoneal injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of K562/A02 xenografts only by 5.8%. No enhancement effect by BrTet was seen in K562 xenografts. It is concluded that BrTet shows significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase intracellular accumulation of anticancer drugs. BrTet may be a promising-MDR modulator for eventual assessment in the clinic.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Benzylisoquinolines ; pharmacology ; Drug Resistance, Multiple ; drug effects ; genetics ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Female ; Humans ; K562 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays