Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro

TRAIL is a novel therapeutic agent for potential use in glioblastoma multiforme therapy; however, glioblastoma multiforme cells exhibit resistance to TRAIL-induced apoptosis. To evaluate the effects of cisplatin on sensitivity of human glioma cell line U251 to Ad-TRAIL and to investigate the potential mechanism, U251 cells were transfected with Ad-TRAIL and then exposed to cisplatin. The proliferation inhibition of the treated cells was studied by the method of MTT. The cell apoptosis was analyzed by Hoechst33342 staining and by flow cytometry with propidium iodide staining. Semi-quantitative RT-PCR was introduced to detect the mRNA expression of TRAIL, DR4, DR5, Caspase 3, and survivin. Protein expression of DR5 and cleaved Caspase 3 was detected by Western blot assay. The results showed that the combination treatment of cisplatin and Ad-TRAIL could inhibit the proliferation of U251 cells significantly compared with the alone treatment (P < 0.01), which was chiefly attributed to the induction of obvious apoptosis. The enhancement of Ad-TRAIL by cisplatin was due to the up-regulation of DR5 but not DR4 expression, and followed by the down-regulation of survivin and activation of Caspase 3. In conclusion, cisplatin could enhance the apoptosis induction of U251 cells to adenovirous vector carried TRAIL.