Harnessing Focal Adhesions to Accelerate p53 Accumulation and Anoikis of A549 Cells Using Colloidal Self-Assembled...

Extracellular matrix (ECM) of the tumor microenvironment (TME), including topography and biological molecules, is crucial in cancer cell attachment, growth, and even the sensitivity to the chemo and cell drugs treatment. This study hypothesizes that mimic ECM structures can alter the attachment and drug sensitivity of cancer cells. A family of artificial ECM called colloidal self-assembled patterns (cSAPs) was fabricated to mimic tumor ECM structures. Cell adhesion, proliferation, and drug sensitivity of the A549 non-small cell lung cancer (NSCLC) cells were studied on 24 cSAPs, named cSAP#1-cSAP#24, where surface topography and wettability were distinct. The results showed that cell adhesion and cell spreading were generally reduced on cSAPs compared to the flat controls. In addition, the synergistic effect of cSAPs and several chemo drugs on cell survival was investigated. Interestingly, A549 cells were more sensitive to the combination of doxorubicin and cSAP#4. Under this condition, the focal adhesion kinase (FAK) signaling was downregulated while p53 signaling was upregulated, confirmed by real-time PCR and western blot analysis. It indicates that the specific surface structure could induce higher drug sensitivity and in vitro anoikis of A549 cells. A serum alternative, human platelet lysate (hPL), and different cSAPs were examined to verify our hypothesis. The result further confirmed that cell adhesion strongly affected the drug sensitivity of A549 cells. This study demonstrates that the tumor ECM is vital in cancer cell activity and drug sensitivity; therefore, it should be considered in drug discovery and therapeutic regimens.