PDCD5Gene Sensitizes Lung Cancer Cells To Cisplatin-induced Apoptosis In Vitro And In Vivo

Objective:This study intends to explore PDCD5gene for cisplatin-induced apoptosis of A549cells and possible mechanisms in vivo and in vitro.Methods:Part1:Transfects the pcDNA3.1-PDCD5recombinant plasmid into A549cells by lipofectamine2000.Its expression were observed by RT-PCR. The effects of cisplatin in combination with PDCD5on the proliferation and apoptosis of A549cells were measured by MTT analysis and flow cytometry.The espression of PDCD5、 Bcl-2and Survivin protein were examined by Western bolt.Part Ⅱ:The model of human lung carcinoma transplanted subeutanegusly was established in25nude mice, then divided randomly into five groups:control (N-null) group, liposome-pcDNA3.1(lip-null) group, liposome-PDCD5(lip-PDCD5) group, cisplatin (DDP) and combination therapy (PDCD5+DDP) group. The tumor growth was observed and measured.The apoptosis rate of A549cells were measured by TUNEL,then caculated the apoptosis index(AI). Theexpression of PDCD5, Bcl-2, Survivin protein were measured by immunohistochemical assay.Results:1.RT-PCR showed that PDCD5was successfully transfected into A549cells, and the expression of PDCD5mRNA in A549A549/PDCD5group was significantly higher than the group in A549/neo group. There is a statistically significant difference in two groups. The cells’apoptosis rate in A549/PDCD5group was significantly higher than in A549/Neo group and A549groups in combination with cisplatin treatment. Western blot analysis showed, expression of PDCD5protein was significantly higher than in A549/PDCD5A549group than A549group and A549/neo group,whereas the expression of Bcl-2and Survivin is reduced.2.Compared with other four groups, the PDCD5+DDP group’s turner volume was significantly reduced(P<0.05), and AI was significantly higher(P<0.05).Mouse treated with PDCD5had an higher expression of PDCD5protein and lower expression of Bcl-2and Survivin protein than other groups(P<0.05).Conclusion:PDCD5gene can significantly inhibite the growth of A549cells and induce them to apoptosis, possibly through decreasing the expression of Bcl-2and Survivin gene to inhibite the development of lung cancer in a dose and time-dependent manner. Whereas, PDCD5gene sensitizes A549cells to cisplatin-induced apoptosis,and provide a new method for genetherapy.