Paclitaxel Exerts Anti-tumor Effects By Inducing Autophagic Death Of Gastric Cancer Cells And Cooperating With Apoptosis

OBJECTIVE:Cytotoxicity tests showed that paclitaxel(Ptx)has good anti-tumor effect on gastric cancer cell lines SGC-7901 and BGC-823,but there is a significant difference between the number of dead cells and apoptotic cells.This experiment is to study whether Ptx induced autophagic death synergistic cell apoptosis.METHODS:MTT assay,AO/EB staining and flow cytometry were used to analyze gastric cancer cell death with Ptx.Lyso Tracker Red probe and DAPI fluorescently stained gastric cancer cells were observed by fluorescence microscope.Ptx concentration and intracellular acidic organelle formation were analyzed.The autophagic flow in gastric cancer cells transfected with Cherry-EGFP-LC3B was observed,and the relationship between Ptx concentration and autophagosome formation was analyzed.The protein expression levels of apoptosis markers and autophagy markers were detected by Western blotting.The relationship of apoptosis and autophagy was analyzed with Ptx.RESULTS:High concentration of Ptx resulted in more apoptosis of gastric cancer cells,more eosinophilic stained organelles and stronger autophagic flow;high concentrations of Ptx induced more apoptotic markers Bax and autophagy markers LC3II and Beclin 1 expression.CONCLUSIONS:Ptx can induce apoptosis and autophagic cell death in gastric cancer cells,and it can induce the increase of autophagosomes and autophagic flux.It may synergistically exert anti-tumor effects by inducing apoptosis and autophagic death.The mechanism of Ptx in the treatment of gastric cancer provides a new explanation and may provide a new approach for the treatment of gastric cancer.Objective To evaluate the clinical application of enteral nutrition by nasojejunal tube insertion and by percutaneous endoscopic gastrostomy(PEG)in elderly patients.Methods A total of 65 elderly patients with dysphagia recruited at our department from January 2010 to November 2014 were divided into the nasojejunal tube feeding groups(35 cases)and the PEG feeding group(30 cases).Differences between these two groups in nutritional indexes,immunological indexes,complications and mortality were analyzed retrospectively.Results Serum total protein,albumin and prealbumin and upper arm circumferences all increased after treatment with nasojejunal tube feeding or percutaneous endoscopic gastrostomy(P>0.05).There was overall improvOTient in nutritional status,as assessed by Nutritional Risk Screening 2002(NRS2002).Specifically,the before/one monsth-after treatment ratio of scores was3.72±0.91/1.9±0.61(t=7.24,P<0.01)for the nasojejunal tube feeding group and3.52±1.23/2.02±0.53(t=4.17,P<0.01)for the PEG feeding group.Compared with NRS2002 scores at one month post-operation,further improvement was achieved at3 months post-operation both for the nasojejunal tube feeding group(1.89±0.65?t=5.21,P<0.01)and for the PEG feeding group(1.91±0.62,t=4.40,P<0.01).There was no difference in the indexes of nutrition,immirne status or mortality between the two groups(P>0.05).Although improvement in CD3+,CD4+,CD8+,CD4+/CD8+,IgA,Ig G,and Ig M was seen in both groups after operation,the differences did not reach statistical significance(P>0.05).The incidence of aspiration pneumonia was notably lower(P<0.05)while the incidence of diarrhea was much higher(P<0.05)in the nasojejunal tube feeding group than in the PEG feeding group at one month and three months.The two groups had similar causes of death and mortality rates.Conclusion Both nasojejunal tube and PEG feeding can improve the nutritional status of elderly patients with dysphagia.However,the choice for the route of nutrition should be individualized.