The Research Of Combined Application Of Recombinant Human Endostatin And Paclitaxel Suppresses Gastric Cancer Cells And Relevant Mechanism

ObjectiveThis study aimed to observe the effect of combined application of endostar andpaclitaxel on growth of gastric cancer cell lines. And by this research to verify thetreatment efficacy and explore the further mechanism, which may provide theoreticalbasic for the application in clinic.Methods(1) Human gastric carcinoma MGC803cells were used as in vitro models. Theanti-proliferation activities of endostar and paclitaxel single-agent in differentconcentrations and times were detected via MTT assay, and determine the optimal dose.Gastric carcinoma MGC803cells was divided into four groups: control group,paclitaxel groups, endostar groups and combination groups.(2) MMT assay was used toexamine the inhibition rate of cell growth when cells were treated at variousconcentrations of endostar and paclitaxel alone or in combination.Then the coefficientof drug in interaction (CDI) was used as a quantitative measure of the degree ofinteraction between different drugs.(3) Annexin V FITC/PI double marking stainingmethod to detect the characteristics of cell apoptosis.(4)Invasion ability was examinedby Transwell assay.(5) The level of VEGF and MMP-2were detected by ELISA assay.(6) The protein expressions of VEGF，MMP-2and MMP-9were examined by Westernblot.Result(1) Endostar or paclitaxel effectively inhibited the growth of MGC803cells, paclitaxelgroups and combination groups observed the concentration and time dependent manner,however, endostar groups only observed the concentration dependent manner.(2) Endostar and paclitaxel effectively promote MGC803cells apoptosis in aconcentration-dependent manner and the effects were enhanced when they combined.(3)Endostar and paclitaxel effectively inhibited the invasion ability of MGC803cells in aconcentration-dependent manner. And the role of inhibition in combination groups isobvious.(4) The level of VEGF and MMP-2expression were reduced in paclitaxel andendostar groups, and the decrease was more obvious in combination groups.(5)Compared with control group, the VEGF, MMP-2and MMP-9protein expression wasdecreased in experimental groups, and the reduction was more obvious when theycombined.ConclusionIn vitro experiment, endostar combine with paclitaxel inhibited the proliferation andinvasion ability of MGC803, at the same time, inducted gastric carcinoma MGC803cells apoptosis in complementary relationship. Endostar significantly reduced the abilityof MGC803through the reconstruction basement membrane in the concentrationdependent manner. The level of VEGF and MMP-2expression were reduced inpaclitaxel and endostar groups, and the decrease was more obvious in combinationgroups. The two drugs also decreased the level of VEGF, MMP-2and MMP-9proteinexpression, and the reduction was more obvious when they combined. With the increaseof drugs concentration, the level of cytokines and protein more decreased, and theinvasion and metastasis ability of MGC803cells more reduced. Endostar combinedwith paclitaxel can suppress the invasion of MGC803cells and decreasing VEGF,MMP-2and MMP-9expression may be the related mechanism.