Combination Therapy Promotes Apoptosis of Melanoma Cells
Metastatic self-protection pathway, activated by cisplatin alone, can be overcome
WEDNESDAY, Oct. 3 (HealthDay News) -- Simultaneous treatment of melanoma with a combination of the chemotherapy agent cisplatin and the mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) may thwart chemoresistance that occurs with treatment of cisplatin alone, according to a report published in the September issue of the Journal of Investigative Dermatology.
Alireza Mirmohammadsadegh, Ph.D., of Heinrich-Heine-University in Dusseldorf, Germany, and colleagues extracted samples of melanoma metastases and cell lines (BLM, MV3, M13 and A375) from several human volunteers. These were exposed to U0126 and cisplatin, after which apoptotic cells were quantified.
When melanoma cell lines were treated with cisplatin alone, enhanced chemoresistance was observed through increased levels of phosphorylated extracellular signal-regulated kinase, leading in turn to activation of the cell survival protein 90-kDa ribosomal S6 kinase. Administration of U0126 served to block this effect in most of the observed cell lines, resulting in a significant decrease in cell survival and proliferation by encouraging cisplatin-induced apoptosis. This effect was observed to be especially strong at lower concentrations of cisplatin for most cell lines investigated.
"Further investigation on the mechanism of how the epidermal growth factor pathway activates extracellular signal-regulated kinase and studying its inhibition in combination with anti-cancer drugs may be helpful in improving melanoma therapy," the authors conclude.