Pt NCs-Based Chemotherapeutic Agents Significantly Induce The Apoptosis Of The Non-Small Cell Lung Cancer A549 Cells And Cisplatin-Resistant A549/DDP Cells With The Expression Of P53

PurposePolyethyleneimine caged platinum nanoclusters(PEI-caged Pt NCs)chemotherapy drug were proposed as a new chemotherapeutic agent to apply in the treatment of non-small cell lung cancer(NSCLC),to evaluate the effect of Pt NCs chemotherapy drug on cell proliferation,cell apoptosis and the relationship between p53 protein expression.To exploring the possible mechanism of the Pt NCs chemotherapy drug overcome cisplatin resistance in NSCLC cells,which provide a new therapeutic idea for chemotherapy of cisplatin-resistant non-small cell lung cancer.MethodsThe effects of Pt NCs chemotherapy drug on A549 cells and cisplatin resistant A549/DDP cells were observed by confocal microscopy.CCK-8 assay was used to analyze the proliferation inhibition effect of cisplatin and Pt NCs chemotherapy drug on of A549 cells and A549/DDP cells.Annexin V-FITC/PI assay was used to detect the apoptosis effect of Pt NCs chemotherapy drug on A549 cells and A549/DDP cells.The expression of p53 protein in A549 cells and A549/DDP cells after Pt NCs chemotherapy drug treated was explore through Werstern bolt.Results1.Through the results of the confocal microscopic images,we found that Pt NCs chemotherapy drug can enter both cell nuclei and cytoplasm in A549 cells and A549/DDP cells after 4 h co-culture.It is interesting to notice that Pt NCs2.chemotherapy drug preferably enter almost cell nuclei in the cisplatinresistant A549/DDP cells groups.3.After the different concentration of Pt NCs chemotherapy drug(0,0.5,1.25,2.5,5.0 μg/mL)treated with cisplatin-resistant A549 cells for 24 h,the proliferation inhibition rate of A549 cells gradually increased(12.47%,55.09%,82.24%,92.29%)with the Pt NCs chemotherapy drug concentration increased.And compared with the cisplatin group,treat group had statistical significance(P<0.05).4.After the different concentration of Pt NCs chemotherapy drug(0,2.5,5,10,20 μg/mL)treated with cisplatin-resistant A549/DDP cells for 24 h,the proliferation inhibition rate of A549/DDP cells gradually increased(57.58%,91.49%,96.69%,95.93%)with the Pt NCs chemotherapy drug concentration increased.And compared with the cisplatin group,Pt NCs chemotherapy drug5.group had statistical significance(P<0.001).6.After the different concentration of Pt NCs chemotherapy drug(0,1,3,5 μM)treated with A549/DDP cells and A549 cells for 24 h,the cell apoptosis rate gradually increased(A549 cells group: 4.21%,58.12%,60.14%,79.74%.A549/DDP cells group: 3.31%,51.93%,76.7%,81.29%)with the Pt NCs chemotherapy drug concentration increased.7.After the different concentration of Pt NCs chemotherapy drug(0 μM,1 μM)treated with A549/DDP cells and A549 cells for 24 h,the increased expression of p53 protein in the treatment group(1 μM)was statistically significant compared with the control group(0 μM)(P<0.05).Conclusion:1.Pt NCs not only inhibit cells’ proliferation and promote apoptosis of non-small cell lung cancer cells,but also has the function of fluorescence labeling.2.Compared with cisplatin,Pt NCs significantly inhibit the proliferation of non-small cell lung cancer cells and overcome cisplatin resistance.3.Pt NCs induce the apoptosis of NSCLC A549 cells and cisplatin-resistant NSCLC A549/DDP cells by up-regulating the expressiong of p53 protein.p53-related signaling pathways may participate in the process of apoptosis and reversal of cisplatin resistance.