Effect of sub-toxic concentrations of cisplatin on caveolin-1 expression and anoikis in lung cancer cells

Abstract

Cisplatin-based chemotherapy, in certain cases, is followed by enhanced progression or increased aggressiveness of cancers. Because the molecular basis of such phenomenon is largely unclear, this study thus investigated the possible impact of cisplatin exposure on anoikis characteristics of human lung carcinoma H460 cells. Cells were treated with sub-toxic concentrations of cisplatin for 24 h, followed by detachment, and examined for viable cells. We found that cisplatin exposure caused cells to resist anoikis in a dose-dependent manner. The attenuation of cell anoikis was found to be tightly associated with the elevation of caveolin-1 (Cav-1) level in these cells. Cav-1 transfected (H460/Cav-1) cells were demonstrated in the present study to exhibit high anoikis resistance whereas ShRNA Cav-1 transfected (H460/shCav-1) cells expressed opposite behavior. Further, This study found that reactive oxygen species (ROS)-induced by cisplatin played a key role on such Cav-1 up-regulation. Cellular superoxide anion and hydrogen peroxide were up-regulated in response to cisplatin treatment; however, only hydrogen peroxide was found to induce Cav-1 elevation. Together, This findings demonstrate the novel effect of sub-toxic cisplatin treatment on cancer cells which may lead to a better understanding of cancer biology and the improvement of chemotherapy.