engleski

A dual role of p21waf1/cip1 gene in apoptosis of HEp-2 treated with cisplatin or methotrexate

We investigated the effects of p21waf1/cip1 gene over-expression in human laryngeal squamous carcinoma cells HEp-2 lacking p53 protein expression on apoptosis induction upon the treatment with two commonly used chemotherapeutic agents, cisplatin and methotrexate. For that purpose, we employed cDNA-arrays and qPCR to monitor gene expression upon treatment with AdCMV-p21 alone or in combination with the chemotherapeutic compounds. We found that p21waf1/cip1 gene over-expression provoked apoptosis of HEp-2 through the induction of the TNFRSF9 gene and activation of caspase 7. Additionally, we have proved that p21waf1/cip1 can assume a dual role in apoptosis in the same cell system depending on the chemotherapeutic agent: its over-expression enhances apoptosis in cisplatin-treated cells and attenuates apoptotic signals in methotrexate-treated cells. The observed dual role of p21waf1/cip1 was in direct correlation with the modulation of caspase 3 and 7 activation and changes in the expression of GADD45a gene. The results presented herein encourage future use of targeted p21waf1/cip1 gene therapy in cancer treatment in a well-defined therapeutic and genetic context.

Apoptosis ; GADD45a ; p21waf1/cip1 ; HEp-2 cells ; cisplatin ; methotrexate

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