Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro |
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Authors: | Jian Chen Xiaobai Sun Weihua Yang Guosheng Jiang Xingang Li |
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Institution: | (1) Department of Neurosurgery, Jining First People’s Hospital, Jining Medical College, Jining, 272011, Shandong Province, China;(2) Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China;(3) Key Laboratory for modern medicine and technology of Shandong province, Key medical laboratory for tumor immunology & Chinese medicine immunology of Shandong province, The Institute of basic medicine, Shandong Academy of Medical Sciences, Jinan, 250062, People’s Republic of China; |
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Abstract: | 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. |
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