3D spheroid-microvasculature-on-a-chip for tumor-endothelium mechanobiology interplay.

During the final stage of cancer metastasis, tumor cells embed themselves in distant capillary beds, from where they extravasate and establish secondary tumors. Recent findings underscore the pivotal roles of blood/lymphatic flow and shear stress in this intricate tumor extravasation process. Despite the increasing evidence, there is a dearth of systematic and biomechanical methodologies that accurately mimic intricate 3D microtissue interactions within a controlled hydrodynamic microenvironment. Addressing this gap, we introduce an easy-to-operate 3D spheroid-microvasculature-on-a-chip (SMAC) model. Operating under both static and regulated flow conditions, the SMAC model facilitates the replication of the biomechanical interplay between heterogeneous tumor spheroids and endothelium in a quantitative manner. Serving as anin vitromodel for metastasis mechanobiology, our model unveils the phenomena of 3D spheroid-induced endothelial compression and cell-cell junction degradation during tumor migration and expansion. Furthermore, we investigated the influence of shear stress on endothelial orientation, polarization, and tumor spheroid expansion. Collectively, our SMAC model provides a compact, cost-efficient, and adaptable platform for probing the mechanobiology of metastasis.

Resveratrol reverses multidrug resistance in human breast cancer doxorubicin-resistant cells.

Although its mechanisms remain unidentified, resveratrol (trans-3,4',5-trihydroxystilbene; RES), which is an active, low molecular-weight compound, possesses a unique antitumor function and is capable of enhancing the cytotoxicity of doxorubicin (DOX) within solid tumor cells. RES is hypothesized to exert these effects by reversing the multidrug resistance (MDR) of the cancer cells in response to chemotherapeutic agents. The aim of the present study was to investigate the reversal effect of RES on MDR in human breast cancer DOX-resistant (MCF-7/DOX) cells and investigate the underlying mechanisms of RES. The results demonstrated that RES inhibited the proliferation of MCF-7/DOX and MCF-7 cells in a dose-dependent manner. Moreover, RES enhanced the cytotoxicity of DOX on MCF-7/DOX cells and the reversal index of RES treatment was demonstrated to be significantly higher when compared with that of the group without RES treatment. In addition, RES was observed to reverse the MDR of the MCF-7/DOX cells and elevate the concentration of DOX in the MCF-7/DOX cells. Furthermore, RES was identified to significantly downregulate the MDR-1 gene and P-glycoprotein expression levels. Reversing MDR, via the downregulation of MDR-1 expression, was concluded to be a mechanism of RES, which enables the unique antitumor function of this polypeptide. Therefore, the present study indicated that RES may be a novel MDR reversal agent for the treatment of breast cancer.