Galina Ivanivna Solyanik

Cell mechanical properties are fundamental to numerous cellular functions, including growth, division, motility, adhesion, and responsiveness to pharmacological treatments. The mechanics of cellular components collectively contribute to overall cell mechanical behavior. Structures such as the membrane, cytoskeleton, nucleus, and other organelles constitute an interconnected network that is central to the mechanobiology of individual cells. During the progression of tumor cells to a metastatic phenotype, significant alterations in mechanical properties occur, playing a pivotal role in this transformation. To model metastasizing tumor cells, cultivation under deadhesive conditions has been employed. In this study, two cell lines with distinct metastatic potentials — Lewis lung carcinoma (LLC) and LLC/R9 — were cultured under either adhesive (representing typical tumor cells) or deadhesive (representing metastatic tumor cells) conditions. The quantitative assessment of cell mechanical properties was found to depend upon the cell cycle phase, measurement technique, and theoretical modeling approach. This article examines alterations in mechanical properties, specifically membrane tension and elastic shear modulus, in circulating metastatic tumor cells as determined via micropipette aspiration. Results indicate that cells grown under deadhesive conditions exhibit greater population homogeneity and a narrower distribution of elastic shear modulus values compared to those grown under adhesive conditions. Furthermore, LLC cells demonstrated lower elastic shear moduli than LLC/R9 cells, correlating with their respective metastatic activities. These mechanical parameters may serve as valuable markers for determining the metastatic potential of tumor cells.

Lactate dehydrogenase (LDH) is a key glycolytic enzyme that catalyzes the interconversion of pyruvate and lactate, with LDHA gaining particular attention for its overexpression in various malignancies and pivotal role in the Warburg effect-driven metabolic reprogramming. Elevated LDHA activity supports rapid ATP production under hypoxic conditions, maintains NAD⁺ regeneration, and promotes lactate accumulation, creating an acidic tumor microenvironment (TME) that favors invasion and immune evasion. Accumulating evidence demonstrates that LDHA is essential for primary tumor growth and critically involved in circulating tumor cell (CTC) survival, anoikis resistance, and metastatic spread. These functions are mediated by its regulation of adhesion molecules, cytoskeletal remodeling, and energy adaptation that enable CTCs to withstand mechanical shear stress and immune surveillance in the bloodstream. Pharmacological inhibition of LDHA, particularly via sodium oxamate (oxamate), has shown substantial potential in reducing metastasis and enhancing chemotherapy sensitivity in preclinical models. Oxamate has emerged as a promising candidate for metabolic cancer therapy due to its unique double effects on tumor metabolism and anti-tumor immunity, which are an advantage rarely highlighted in broader LDHA-focused reviews. This review synthesizes the molecular mechanisms through which LDHA drives tumor progression, dissects its context-specific functions in CTC biology, and evaluates the translational potential of LDHA-targeted strategies, with a focused emphasis on oxamate, as a transformative anti-metastatic therapeutic paradigm. By filling a critical gap in synthesizing oxamate’s distinct metabolic–immune regulatory actions, this work addresses an unmet need in the management of advanced, treatment-refractory cancers.

Journal of Medicinal Plants for Economic Development

Background: Microscopy is a key tool in biophysical research for visualizing living cells' morphology, structure, and dynamic processes. Depending on the specific research goals, various optical and electron microscopy techniques can be applied, each offering unique benefits. Determining the structural features of the cytoskeleton, nucleus, and membrane of circulating tumor cells in the model Lewis lung carcinoma (LLC) is an important biophysical and biological task, as it will allow identifying targets for antitumor and antimetastatic therapy, as well as investigating the mechanisms of action of antitumor drugs. However, comprehensive multimodal imaging of such cells — particularly under non-adherent conditions — remains limited in the literature due to the difficulty of working with such models. Objectives: This study aimed to visualize Lewis lung carcinoma (LLC) cells cultured under de-adhesive conditions using various microscopy techniques for their characterization and to examine the cancer cells' structure and functionality. The goal was to evaluate each method's individual capabilities and combined strengths in revealing cellular morphology, internal structure, and nanoparticle interactions. Materials and Methods: LLC cells were obtained from the National Bank of Cell Lines and Tumor Strains of the IEPOR (NAS of Ukraine) and cultured in RPMI-1640 medium under conditions of de-adhesive growth. Imaging was performed using inverted optical microscopy (Euromex Oxion), fluorescence and confocal microscopy (Carl Zeiss LSM 510) with F-actin (Alexa Fluor 488-phalloidin) and nuclear (Hoechst 33342) staining, and label-free Coherent Anti-Stokes Raman Scattering (CARS) microscopy (Leica TCS SP8). Scanning electron microscopy (TESCAN MIRA3 LMU) was used for high-resolution surface imaging. 2D-MoS₂ nanoparticles, as well as 2D-MoS₂ and doxorubicin simultaneously, were applied to investigate nanoparticle-mediated labeling and cellular uptake. Results: A comparative analysis of multiple imaging modalities — including optical, fluorescence, confocal, CARS, and SEM — was applied to Lewis lung carcinoma (LLC) cells. Fluorescence microscopy with specific fluorophores made it possible to analyze the size and properties of actin fibers and showed that nuclei occupy most of the deadhesive cells. Electron microscopy revealed numerous filopodia on the cell surface. CARS showed the presence of lipid droplets in the cells. Conclusions: Each microscopy method provided complementary insights into cell morphology, cytoskeletal organization, lipid content, and surface ultrastructure. Nanoparticles demonstrated high utility as dual imaging and therapeutic agents. This work represents the first detailed SEM study of non-adherent LLC cells and highlights the potential of integrated multimodal imaging for studying circulating tumor cell models.

Background. The predominance of aerobic glycolysis over oxidative phosphorylation (the Warburg effect) is characteristic of almost all invasive forms of cancer. The specificity of cancer (especially metastatic) cell energy metabolism represents multiple targets for therapeutic intervention using glycolysis inhibitors. Although the transition of cells to the bloodstream (i.e., anchorage-independent growth) is an important step of the metastatic cascade, the question of the cytotoxic efficacy of glycolysis inhibitors against these cells remains largely open. Methods. The cytotoxicity of 2-deoxy-D-glucose, sodium oxamate, metformin, cisplatin, and paclitaxel against high and low metastatic Lewis lung carcinoma cells during anchorage-independent growth (using polyHEMA coated plates) compared to anchorage-dependent growth was studied. The survival, proliferative activity, metabolic plasticity, and FTIR-ATR spectra of the sodium oxamate-resistant cells under different growth conditions were investigated Results. Unlike cisplatin and paclitaxel (which are the basic drugs for the treatment of lung cancer) glycolysis inhibitors such as 2-deoxy-D-glucose and sodium oxamate exhibit high cytotoxicity against carcinoma cells during anchorage-independent growth (compared to anchorage-dependent growth), which correlates with an enhanced glucose consumption rate of these cells. The cytotoxicity of glycolysis inhibitors was shown to be limited by the emergence of resistant cells whose survival was maintained at low glucose consumption rates especially in cells under anchorage-independent growth, most likely due to their ability to activate glutaminolysis. Conclusions. The enhanced cytotoxicity of glycolysis inhibitors against cells during anchorage-independent growth and the emergence of resistant cells, whose survival is presumably related to the activation of mitochondrial metabolism, indicates the potential antimetastatic efficacy of a combination of glycolysis and OXPHOS inhibitors

Metastasis in oncological diseases remains one of the main reasons for negative prognosis regarding treatment. Any new data on the biophysical and biochemical characteristics of circulating metastatic cells will help to develop a concept for antimetastatic therapy. In this study, we found a number of differences in the spectroscopic and morphological features of circulating metastatic cells. FT-IR and Raman spectra cultivated by adhesive and de-adhesive methods (with the latter used as a model for metastatic cells) have shown spectroscopic features, namely in FT-IR spectra in the region of CH stretching vibrations, which are associated with structural rearrangements in the cell membrane, as well as changes in the intensity and position of the PO₂⁻ group vibration bands correlated with proliferative activity. The spectral features in the regions of OH stretching and Amide I vibrations as well as other spectral markers of the metastatic cells grown under different cultivation conditions were derived. Raman spectra showed a redistribution of the amino acid Tyr/Trp (tryptophan to tyrosine) ratio and in Tyr doublet intensity in the region of 500–900 cm⁻¹, as well as varying glycogen levels in different cells. The spectroscopic markers are in accordance with biochemical data. CARS and confocal optical microscopy were applied to determine the state of the cells and the F-actin expression level, which turned out to be higher for adhesive cells in comparison with de-adhesive cells. The shape and the morphological properties of the cells differ drastically. The correlation of vibrational markers with biochemical data and the cytofluorometric method was discussed.

Metastasis in oncological diseases remains one of the main reasons for negative prognosis regarding treatment. Any new data on the biophysical and biochemical characteristics of circulating metastatic cells will help to develop the concept of antimetastatic therapy. In this study we found a number of differences in spectroscopic and morphological features of circulating metastatic cells. FTIR and Raman spectra of cultivated by adhesive and de-adhesive methods (last as a model for metastatic cells) have showed spectroscopic features, namely in FTIR in the region of CH - stretching vibrations associated with structural rearrangements in the cell membrane, as well as changes in the intensity and position of the PO2- group vibrations bands correlated with a proliferative activity. The spectral features in the regions of OH stretching and Amid I vibrations and other spectral markers of the metastatic cells under different cultivation conditions were derived. Raman spectra showed redistribution of amino acid Tyr/Trp ratio and in Tyr duplet intensity in the region of 500-900 cm-1 , as well different glycogen level in different cells. The spectroscopic markers are in the accordance with biochemical data. CARS and confocal optical microscopy were applied for determination a state of the cells and F-actin expression level that turned out to be higher for adhesive cells in comparison with de-adhesive cells. Shape and morphological property of the cells drastically differs. The correlation of vibrational markers with biochemical data and cytofluorometric method were discussed.

Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta‐derived MSCs (P‐MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co‐inoculation of LLC and P‐MSCs (LLC + P‐MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day. This is explained by the fact of a decrease in the secretion of proangiogenic factors during in vitro co‐cultivation of an equal amount of LLC and P‐MSCs. When P‐MSCs are intravenously (i.v.) injected in the mice with developing LLC (LLC + P‐MSCs(i.v.)), the tumor growth and angiogenesis are stimulated on the 15th day. A highly activated secretion of proangiogenic factors by P‐MSCs in a similar in vitro model can explain this. In both the models compared to the control on the 23rd day, there is no significant difference in the tumor growth, while angiogenesis remains correspondingly decelerated or stimulated. However, in both the models, the total volume and number of lung metastases constantly increase compared to the control: it is mainly due to small‐size metastases for LLC + P‐MSCs(i.v.) and larger ones for LLC + P‐MSCs. The increase in the rate of LLC cell dissemination after the injection of P‐MSCs is explained by the disordered polyploidy and chromosomal instability, leading to an increase in migration and invasion of cancer cells. After LLC + P‐MSCs co‐inoculation, the tumor cell karyotype has the most complex and heterogeneous chromosomal structure. These findings indicate a bidirectional effect of P‐MSCs on the growth of LLC in the early periods after injection, depending on the injection method, and, correspondingly, the number of contacting cells. However, regardless of the injection method, P‐MSCs are shown to increase LLC aggressiveness related to cancer‐associated angiogenesis and metastasis activation in the long term.

Introduction. The regularities of the effect of prior electron irradiation of saline solution on the optical and cytotoxic properties of saline solution and doxorubicin dissolved in it are studied in order to increase their cytostatic efficiency. Methods. The energy of the irradiation electrons was equal to 1 MeV, the absorbed dose was within (2...80) kGy. It has been reported that the amount of absorbed radiation dose affects the optical characteristics of saline in the UV, visible, and IR regions. Changes in the extinction spectra of the physiological solution depended on both the absorbed dose and the wavelength of the light. Results. It was established that radiation-induced changes in the extinction properties and cytostatic activity of the irradiated physiological solution last 2-4 months, depending on the amount of the absorbed dose. It is shown that the fluorescence intensity of physiological solution caused by excitation at a wavelength of 260 nm reaches the highest value at the value of the absorbed radiation dose (10...40) kGy. It is shown that the position of the bands of the fluorescence spectra depends on the amount of the absorbed dose. It was established that despite the rearrangement of the fluorescence center, the number of spectral bands due to radiation exposure remains constant. Conclusions. It was shown that pre-irradiation of the FR before dissolving doxorubicin in it leads to an increase in its cytostatic activity. This effect is most pronounced at relatively low concentrations of doxorubicin in the solution. The minimum dose of radiation absorbed by the physiological solution, at which changes in the spectra of the doxorubicin solution are recorded, is 4 kGy.