Enhanced Sensitivity of A549 Cells to Doxorubicin with WS 2 and WSe 2 Nanosheets via the Induction of Autophagy.

The excellent physicochemical properties of two-dimensional transition-metal dichalcogenides (2D TMDCs) such as WS 2 and WSe 2 provide potential benefits for biomedical applications, such as drug delivery, photothermal therapy, and bioimaging. WS 2 and WSe 2 have recently been used as chemosensitizers; however, the detailed molecular basis underlying WS 2 - and WSe 2 -induced sensitization remains elusive. Our recent findings showed that 2D TMDCs with different thicknesses and different element compositions induced autophagy in normal human bronchial epithelial cells and mouse alveolar macrophages at sublethal concentrations. Here, we explored the mechanism by which WS 2 and WSe 2 act as sensitizers to increase lung cancer cell susceptibility to chemotherapeutic agents. The results showed that WS 2 and WSe 2 enhanced autophagy flux in A549 lung cancer cells at sublethal concentrations without causing significant cell death. Through the autophagy-specific RT 2 Profiler PCR Array, we identified the genes significantly affected by WS 2 and WSe 2 treatment. Furthermore, the key genes that play central roles in regulating autophagy were identified by constructing a molecular interaction network. A mechanism investigation uncovered that WS 2 and WSe 2 activated autophagy-related signaling pathways by interacting with different cell surface proteins or cytoplasmic proteins. By utilizing this mechanism, the efficacy of the chemotherapeutic agent doxorubicin was enhanced by WS 2 and WSe 2 pre-treatment in A549 lung cancer cells. This study revealed a feature of WS 2 and WSe 2 in cancer therapy, in which they eliminate the resistance of A549 lung cancer cells against doxorubicin, at least partially, by inducing autophagy.