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Cell mechanics research is making chemotherapy friendlier

Cell mechanics research is making chemotherapy friendlier

Current anti-cancer drugs could be used more effectively and in smaller doses, say scientists from the Institute of Nuclear Physics of the Polish Academy of Sciences in Krakow. They examined the mechanical properties of prostate cancer cells treated with the most widely used drug.

In cancer, the main factor contributing to the formation of metastasis is the ability of the tumor cells to undergo mechanical deformation. At the Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN) in Krakow, research on the mechanical properties of cells has been conducted for a quarter of a century, by informing IFJ PAN in a statement sent to PAP.

The last work was carried out in cooperation with the Department of Medical Biochemistry at the Jagiellonian University School of Medicine (Jagiellonian University School of Medicine), and related to several drugs currently used in chemotherapy for prostate cancer, specifically their effect on the mechanical properties of cancer cells. “The results are optimistic: there are indications that the dosages of some drugs can be reduced without risking a decrease in their effectiveness” – reads the release.

As shown, chemotherapy is a very brutal attack not only on a patient’s cancer cells, but on all cells of his body. With it, doctors hope that the most sensitive cancer cells will die before healthy cells begin to die. In this case, it is necessary to know how to choose the optimal drug in a particular situation and how to determine its minimum dose, which on the one hand will ensure the effectiveness of the treatment, and on the other hand it will reduce the negative effects of treatment.

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Physicists from the Institute of Nuclear Physics PAS already showed in 1999 that tumor cells mechanically deform more easily. In practice, this fact means that they can squeeze through narrow blood vessels and / or the lymphatic system more efficiently.

“The mechanical properties of the cell are determined by the elements of its cytoskeleton such as the microtubules that we study made of the protein tubulin, the actin filaments made of actin and the intermediate filaments made of proteins such as keratin or vimentine” – explains the professor. Doctor Hub. Małgorzata Lekka of IFJ PAN Biophysical Circuits Research Division, quoted in the statement. He adds: “The biomechanical measurements of cells are done using atomic force microscopy. Depending on the needs, we can more or less press the probe on the cell and in this way we obtain a mechanical response coming from the structures either on its surface, i.e. at the cell membrane, or deeper, even in the cell nucleus. However, in order to obtain information about the drug’s effects, we must evaluate the contribution of each type of cytoskeleton fiber to the cell’s mechanical properties.

In the results currently reported, Krakow-based physicists presented experiments using the commercially available DU145 human prostate cancer cell line. This line was chosen – as indicated in the press release – due to its drug resistance. When exposed to long-term drug effects, these cells become resistant to the drugs over time and not only die, but begin to divide.

We focused on the effects of three common drugs: phenflunine, colchicine and docetaxel. They all function on microtubules, which is desirable because these fibers are important in cell division. Docetaxel stabilizes microtubules and thus also increases the hardening of cancer cells and makes it difficult for them to migrate throughout the body. The other two drugs destabilize microtubules, so cancer cells can migrate, but due to the disrupted functions of the cytoskeleton, they are unable to divide. 10.1039 / d0nr06464e).

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Scientists from Krakow analyzed the viability and mechanical properties of cells after 24, 48 and 72 hours of drug treatment, and it turned out that the largest changes were observed three days after exposure to the drug.

The research allowed to identify two concentrations of drugs: higher, which led to the destruction of cells, and lower, where the cells survived, but it was found that their mechanical properties changed. “For obvious reasons, it was particularly interesting what happened with the cells in the latter case. The exact interpretation of some of the results required the use of a number of tools, such as a confocal microscope or a flow cytometry. Their use was possible thanks to the collaboration with the Institute of Pharmacology of the Polish Academy of Sciences In Cracow, Department of Cell Biology at the Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University and University of Milan (Department of Physics, University Degli Studi de Milano) “- Reports IFJ PAN.

“It has been known for some time that when microtubules are damaged, the actin fibers take on some of their functions. Combining measurements of the mechanical properties of cells with images from confocal and fluorescence microscopes allowed us to observe this effect. We were able to pinpoint the areas in the cell that are affected by a particular drug with precision. Understand how its effect changes over time, “confirms PhD student Kubiak.

Practical conclusions can be drawn from the research of physicists from Cracow – for example, the effect of phenflunine is clearly shown in the nuclear region, but it is compensated for by actin fibers. As a result, as shown, the cell remains rigid enough to continue reproducing. On the other hand, after 48 hours of taking the drug, the effects of docetaxel are more pronounced, but mainly on cell margins. This fact also indicates an increased role for actin fibers and means that treatment must be supported with some drugs that act on these fibers.

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To date, there has been little research on the effectiveness of low concentrations of anti-cancer drugs. We show that the problem really deserves attention. Because if we understand the mechanisms of action of individual drugs, we can maintain – and sometimes increase – their current effectiveness while minimizing the side effects of chemotherapy. In this way, chemotherapy may become more suitable for patients, which should affect not only their physical health, but also their mental position, which is absolutely necessary in the fight against cancer ”- concluded Professor K. Light.

PAP – Science in Poland


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