engleski

Inhibition of apoptosis is involved in anti-cancer drug resistance of human laryngeal carcinoma cells

Inhibition of apoptosis may confer resistance of human tumor cells to wide variety of chemotherapeutic drugs with different mode of action. In order to examinewhether this phenomenon is involved in drug resistance of human laryngeal carcinoma (HEp2) cells, we examined and compared induction of programmed cell death in parental cells and drug resistant clones CK2, VK2 and 7T, which had low, but clinically relevant levels of resistance to cisplatin, carboplatin and vincristine, respectively. Two different methods were used to determine the induction of apoptosis: a) counting of cells with characteristic morphological alteration under the fluorescent microscope, and b) the determination of PARP cleavage as an indicator of apoptosis. In order to examine the molecular mechanisms involved in programmed cell death, we investigated constitutive and induced expression of several apoptotic genes by Western blot method. The results show that induction of apoptosis was reduced in drug resistant clones of human laryngeal carcinoma cells. Constitutive expression of apoptotic genes (Bcl-2, Bax, survivin, Fas and Fas L) was mainly not altered but their induced expression did change. In conclusion, our results show that inhibition of apoptosis is involved in resistance of human laryngeal carcinoma cells to selected anti-cancer drugs.

drug-resistance; apoptosis; tumor cells

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