Mechanical Alteration Associated With Chemotherapeutic Resistance of Breast Cancer Cells

BACKGROUND: The mechanical deformability of cancer cells has attracted particular attention as an emerging biomarker for the prediction of anti-cancer drug sensitivity. Nevertheless, it has not been possible to establish a general rubric for the identification of drug susceptibility in breast cancer cells from a mechanical perspective. In the present study, we investigated the mechanical alteration associated with resistance to adjuvant therapy in breast cancer cells. METHODS: We performed an ‘atomic force microscopy (AFM)-based nanomechanical study’ on ‘drug-sensitive (MCF-7)’ and ‘drug-resistant (MCF-7/ADR)’ breast cancer cells. We also conducted cell viability tests to evaluate the difference in doxorubicin responsiveness between two breast cancer cell lines. We carried out a wound closure experiment to investigate the motility changes associated with chemotherapeutic resistance. To elucidate the changes in molecular alteration that accompany chemotherapeutic resistance, we investigated the expression of vinculin and integrin-linked kinase-1–which are proteins involved in substrate adhesion and the actin cytoskeleton–using Western blotting analysis. RESULTS: A MTT assay confirmed that the dose-dependent efficacy of doxorubicin was reduced in MCF-7/ADR cells compared to that in MCF-7 cells. The wound assay revealed enhanced two-dimensional motility in the MCF-7/ADR cells. The AFM mechanical assay showed evidence that the drug-resistant breast cancer cells exhibited a significant decrease in mechanical deformability compared to their drug-sensitive counterparts. The mechanical alteration in the MCF-7/ADR cells was accompanied by upregulated vinculin expression. CONCLUSIONS: The obtained results manifestly showed that the altered mechanical signatures–including mechanical deformability and motility–were closely related with drug resistance in the breast cancer cells. We believe that this investigation has improved our understanding of the chemotherapeutic susceptibility of breast cancer cells.

Nano-mechanical Phenotype as a Promising Biomarker to Evaluate Cancer Development, Progression, and Anti-cancer Drug Efficacy

Since various bio-mechanical assays have been introduced for studying mechanical properties of biological samples, much progress has been made in cancer biology. It has been noted that enhanced mechanical deformability can be used as a marker for cancer diagnosis. The relation between mechanical compliances and the metastatic potential of cancer cells has been suggested to be a promising prognostic marker. Although it is yet to be conclusive about its clinical application due to the complexity in the tissue integrity, the nano-mechanical compliance of human cell samples has been evaluated by several groups as a promising marker in diagnosing cancer development and anticipating its progression. In this review, we address the mechanical properties of diverse cancer cells obtained by atomic force microscopy-based indentation experiments and reiterate prognostic relations between the nano-mechanical compliance and cancer progression. We also review the nano-mechanical responses of cancer cells to the anti-cancer drug treatment in order to interrogate a possible use of nano-mechanical compliance as a means to evaluate the effectiveness of anti-cancer drugs.