| Gastric cancer(GC)is an extremely invasive and heterogeneous lesion,and environmental and genetic factors can contribute to the development of gastric cancer.Because of the symptoms of most patients with early gastric cancer are not significant,they are already in the late stage when they diagnosed,so that they miss the opportunity of surgery and take comprehensive medical treatment as the main treatment.HER2-positive gastric cancer,as a special subtype of gastric cancer,has a poor prognosis and high mortality,so,targeted therapy is its mainly treatment.The To GA test established the status of Trastuzumab in the treatment of HER2-positive gastric cancer,and Trastuzumab has now become the first-line treatment for patients with advanced HER2-positive gastric cancer when used in combination with chemotherapy drugs.However,due to drug resistance and adverse reactions of chemotherapy drugs,its clinical antitumor effect is affected.Nab-paclitaxel is a new formulation of Paclitaxel,which has been widely used in the treatment of various cancers,and has a broad application prospect.However,at present,there are relatively few clinical studies on the treatment of advanced HER2-positive gastric cancer by Trastuzumab combined with Nab-paclitaxel,and the mechanism of action of that therapeutic schedule is still unclear.Therefore,this study observed the effects of Trastuzumab combined with Nab-paclitaxel on the proliferation,activity and apoptosis of human gastric cancer cells NCI-N87 through in vitro experiments,and preliminarily discussed the related molecular mechanism in order to provide a new direction for clinical treatment.Objective: To observe the effects of Trastuzumab combined with Nab-paclitaxel on the proliferation,activity and apoptosis of human gastric cancer cells NCI-N87 and the changes of related protein expression in apoptotic pathway by experiments in vitro.Methods: After reviewing a large number of literatures,the object of this study was identified as human gastric cancer cells NCI-N87 with high expression of HER2 protein.Experimental group and blank control group were set up.The experimental group was composed of monotherapy group included Trastuzumab and Nab-paclitaxel and two drug combination group.Blank control group was cultured with complete culture medium without drugs.The effects of Trastuzumab and Nab-paclitaxel at different concentrations on proliferation of NCI-N87 cells were observed by MTS assay.The effects of two single drug groups and combination group on the activity of NCI-N87 cells were observed by CCK8 assay.Flow cytometry was used to detect the effect of two single drug groups and combination group on apoptosis of NCI-N87 cells.Western blot assay was used to detect the expressions of caspase-3,caspase-8 and PARP-1 in each group.Results:1.MTS result showed that Trastuzumab and Nab-paclitaxel had significant inhibitory effects on NCI-N87 cell proliferation,and the inhibitory effects were concentration-dependent manner(P < 0.05).2.CCK8 result showed that Trastuzumab and Nab-paclitaxel both decreased the activity of NCI-N87 cells(P < 0.01),and the survival rate of NCI-N87 cells further decreased after the combination of the two drugs with a time-dependmenet manner.(P < 0.05).3.Flow cytometry showed that Trastuzumab and Nab-paclitaxel both can induce increased apoptosis of NCI-N87 cells(P < 0.001),and the apoptosis inducing ability of NCI-N87 cells was significantly enhanced after the combination of the two drugs(P < 0.01).4.Western blot result showed that Trastuzumab and Nab-paclitaxel could induce apoptosis of NCI-N87 cells by down-regulating the expressions of caspase-3,caspase8 and PARP-1(P<0.05),and the expression levels of these proteins were further decreased after the combination of the two drugs(P < 0.05).Conclusions:1.Both Trastuzumab and Nab-paclitaxel can inhibit the proliferation of HER2-positive gastric cancer cells NCI-N87 in a concentration-dependent manner.When the two drugs were used in combination,the inhibitory effect was significantly enhanced in a time-dependent manner.2.Trastuzumab combined with Nab-paclitaxel promoted the apoptosis of HER2-positive gastric cancer cells NCI-N87.3.Caspases play a key role in the apoptosis of HER2-positive gastric cancer cells NCI-N87 induced by Trastuzumab combined with Nab-paclitaxel. |
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