Synergistic anti-cancer effects of recombinant adenoviruses DRIL1 and p53 gene transfer against human lung cancer cells
Lung cancer is the most common and most deadly cancer worldwide. Because of the aggressive and metastatic nature of many forms of the disease, it is frequently diagnosed late and responds poorly to the therapies currently available including surgery, radiotherapy, and chemotherapy, have not improved...
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| Format: | Conference or Workshop Item |
| Language: | English English |
| Published: |
2011
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| Online Access: | http://irep.iium.edu.my/4152/ http://irep.iium.edu.my/4152/1/IRIE11-Registration-Dr_Solachuddin-DRIL1.pdf http://irep.iium.edu.my/4152/4/IRIIE2011-KoD_ID_140.pdf |
| Summary: | Lung cancer is the most common and most deadly cancer worldwide. Because of the aggressive and metastatic nature of many forms of the disease, it is frequently diagnosed late and responds poorly to the therapies currently available including surgery, radiotherapy, and chemotherapy, have not improved the survival rates of patients lung cancer. Even, tumors recur in some patients whereas some tumors have become resistant to either chemotherapy or further radiotherapy. For this reason, gene therapy has been developed and considered as a new approach that may effective in combating lung cancers. The application of gene therapy indeed aims for specifically kill cancer cells without disturbing normal cells. We have reported previously that DRIL1, which encodes a member of AT rich interaction domain (ARID) family proteins, is a novel target of tumor suppressor p53 and induced following DNA damage. Here we show that ectopic expression using recombinant adenovirus DRIL1 gene transfer induced transcription of p53-target genes in human non-small cell lung cancer A549 cells in a dose dependent manner. Moreover, these effects were synergistically enhanced by p53 co-expression. Consistently, co-expression of DRIL1 with p53 efficiently induced apoptosis in A549 cells accompanied by augmented activation of genes involved in p53-regulated growth arrest and apoptosis. This study suggest that combination of recombinant adenoviruses DRIL1 and p53 gene transfer may provide an efficient method to treat non-small cell lung cancer. |
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