engleski

avß3 integrin mediated drug resistance in human tongue squamous cell carcinoma

Integrin-mediated drug resistance is based on the adherence of cells to extracellular matrix proteins through integrins. In human laryngeal carcinoma cells a mechanism of multidrug resistance mediated by avß3 integrin have been described. In the present study we investigated whether similar mechanism exists in tongue squamous carcinoma cells (Cal27) which express a small amount of avß3 integrins, and Cal27-derived stable transfectants with increased expression of avß3 integrin. The cell clones were produced by stable transfection of Cal27 cells with a plasmid expressing the ß3 subunit. In one stable transfectant the expression of avß3 was increased but the expression of avß5 remained the same in comparison to parental cell line. The other stably transfected cell line showed an increase in avß3 expression and a moderate decrease in avß5 expression, due to the competition of ß3 for available av in the cell. The sensitivity of Cal27 and Cal27-derived avß3 integrin expressing clones to anti cancer drugs was determined using MTT assay. Our results showed that both Cal27-derived avß3 integrin expressing cell lines were resistant to cisplatin, doxorubicin and mitomycine C. This thesis shows that increased avß3 integrin expression can protect cells from various citostatics. Thus measuring the expression of avß3 integrin in head and neck cancer cells could be an important indicator of tumor resistance to anti-cancer drugs.

integrin-mediated drug resistance

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