As an inhibitor of microtubule assembly, combretastatin A-4 (CA-4)-induced biological responses in tumor cells have been well known, but the corresponding changes in nano-biophysical properties were not investigated given the lack of an ideal tool. Using AFM technique, we investigated the alteration of nano-biophysical properties when CA-4-treated tumor cells underwent the different biological processes, including cell cycle arrest, apoptosis and autophagy. We found that CA-4-resistant cells were rougher with the presence of characteristic “ridges”, indicating that the development of “ridge” structure may be a determinant of the sensitivity of cells to CA-4 compounds. CA-4 induced G2/M arrest and apoptosis in sensitive cells but triggered anti-apoptotic autophagy in resistant cells. CA-4 treatment caused an increase in stiffness in both sensitive and resistant cells. However, these cells exhibited different changes in cell surface roughness. CA-4 decreased Ra and Rq values in sensitive cells but increased these values in resistant cells. The reorganization of F-actin might contribute to the different changes of nano-biophysical properties in CA-4-sensitive and–resistant cells. Our results suggest that cellular nano-biophysical properties, such as “ridges”, roughness and stiffness, could be applied as potential biomarkers for evaluating CA-4 compounds, and knowledge regarding how biological alterations cause changes in cellular nano-biophysical properties is helpful to develop a new high-resolution screening tool for anti-tumor agents.

Background: Inflammation and oxidation stress are key factors in the mechanism of acute lung injury (ALI). Therefore, suppression of the inflammatory response and oxidative stress could be a potential strategy to treat lipopolysaccharide (LPS)-induced ALI. Ginsenoside Rd (Rd), a natural Ginseng extract, alleviates inflammation and oxidative stress in several diseases such as Alzheimer's disease and cerebral ischemia, but its effect on ALI is still unclear. Aims and Objectives: To explore the protective effect of Rd on LPS-induced ALI and explored associated mechanisms. Materials and Methods: Mice were divided into five groups: A sham-operated group, a LPS-induced ALI group, and three LPS groups pretreated with Rd doses of 20, 40, and 80 mg/kg, respectively. The pathological changes of lung, collagen deposition, pulmonary edema, inflammatory cytokine, oxidative stress and the expression levels of TLR4 and NF-κB were detected. Results: The oral administration of Rd dose dependently attenuated histopathologic changes in the lung, lung edema, pulmonary collagen deposition, protein concentration in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activity, and inflammatory cell infiltration. In addition, Rd suppressed the LPS-induced inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1 β in BALF. The productions of oxidative stress-related enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in lung tissue were significantly upregulated by Rd administration. However, malondialdehyde and pulmonary MPO activity was reduced in the Rd-pretreated groups when compared with LPS-induced ALI group. Rd treatment also dose dependently suppressed LPS-induced NF-κB activation and TLR4 expression. Conclusion: Overall, these findings provide evidence that Rd pretreatment inhibits LPS-induced ALI through anti-inflammatory and antioxidative actions, suggesting that it could be a promising protective drug for LPS-induced ALI.