Melanoma is an aggressive disease with the highest death rate within cutaneous malignancies. One of the reasons for it is tumor heterogeneity and the formation of subclones with different sensitivity to anti-cancer therapy. This study was aimed to evaluate the response of melanoma cells from different tumor sites to dacarbazinetreatment. Two fragments of primary melanoma from 35-years-old female patient were isolated and cultured: from the central and peripheral part of the tumor. The cells were treated with different concentrations of dacarbazine followed by cell viability/proliferation estimating using MTT-test. It was shown that cells from central and marginal sites had similar sensitivity to the treatment and demonstrate 50% loss of viability at the concentration of dacarbazine 885.0 µg/mL and 792.5 µg/mL respectively (according to linear approximation). Further we evaluated the effect of 1000 µg/mL of dacarbazine on cell apoptosis, migration and invasion. Dacarbazine treatment induced 30% decrease of alive melanoma cells originated from the central part of the tumor but 5.4% only alive melanoma cells from marginal zone.62.2% cells from the center of tumor were observed at the early apoptosis stage while 54.5% cells from marginal zone were at later apoptosis/necrosis. Migration and invasive capacities were increased in melanoma cells originated from central part of the tumor after incubation with 1000 µg/mL of dacarbazine while melanoma cells from peripheral part diminished their ability to migration and invasion after dacarbazine incubation. Our study demonstrates different sensitivity to dacarbazine of melanoma cells depending on tumor site that could be due to heterogenic pattern of tumor cells and need to be considered for melanoma treatment administration.

Diverse sensitivity of melanoma cells originated from various parts of the tumor to dacarbazine treatment