Abstract

Betel quid chewing is the main cause of oral squamous cell carcinoma (OSCC) has been proved by epidemiological studies in Taiwan. In this study we investigate the expression and the role of vimentin in radiation therapy within an oral carcinoma 3 (OC3), was established from an OSCC in a long-term betel quid chewer who does not smoke. The enhanced expression of vimentin was found in irradiated OC3 cells. We investigated the role of vimentin in oral squamous cell carcinoma cells with RNA interference strategy. The radio-sensitivity response of OC3 cells was clarified by colony formation assay and FITC Annexin V flow cytometric analysis. The cell cycle arrest effect was evaluated by propidium iodide (PI) staining flow cytometric analysis. The transcriptional factor of vimentin was checked by decoy ODN and promoter assay. The role of vimentin was confirmed by transfection of antisense oligonucleotides against p21 into OC3 cells. Our data revealed that vimentin which plays a significant role in supporting and anchoring the position of the organelles in the cytosol was induced in irradiated OC3 cells. We found the enhancement of radio-sensitivity effect in OC3 cells with vimentin siRNA treatment. The vimentin protein was inhibited in OC3 cells with NF-kB inhibitor PDTC pretreatment prior irradiation. The result revealed that NF-kB is one of the transcriptional factors of radiation induced vimentin. To inhibit the expression of vimentin with specific siRNA in OC3 cells, the radio-sensitivity effect and cell cycle arrest effects were observed, the result demonstrated that expression of vimentin is critically involved in the cell cycle arrest effect in OC3 cells while irradiated. Taken together, the results demonstrated that the radiation induced vimentin expression is related with the evading radiation induced apoptosis in betel quid chewing related oral squamous cell carcinoma cells. Irradiation induced NF-kB dependent vimentin expression is related with the evading radiation induced apoptosis in betel quid chewing related oral squamous cell carcinoma cells, down regulation of vimentin may be an important therapeutic strategy in oral squamous cell carcinoma radiation therapy.

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