HUMAN MICROBIOTA AND BREAST CANCER.

Breast cancer is the leading malignancy in women worldwide. To date, much is known about the molecular subtypes of these malignant neoplasms and the mechanisms of drug resistance. Significant success has been achieved in approaches to early diagnosis, which allows identifying the tumor process in the early stages of development. Recently, the study of the influence of the human body microbiota on cancer development and the effectiveness of treatment has become an actively developing field of research. This review presents an analysis of the literature data on this issue.

BIOMAGNETISM OF DRUG-SENSITIVE AND DRUG-RESISTANT MALIGNANT TUMORS AFTER INJECTION OF FERROMAGNETIC NANOCOMPOSITE.

Magnetic signals emitted by living organisms, regardless of a biological species, are important biophysical indicators. The study of these indicators is very relevant and promising for the visualization of the tumor process and the development of technologies using artificial intelligence when it comes to malignant neoplasms, particularly resistant to chemotherapy. AIM: To measure magnetic signals from transplantable rat tumors and their counterparts resistant to cytostatics for evaluating the features of the accumulation of iron-containing nanocomposite Ferroplat. MATERIALS AND METHODS: Doxorubicin (Dox)-sensitive and Dox-resistant Walker-256 carcinosarcoma and cisplatin-sensitive and cisplatin-resistant Guerin's carcinoma transplanted in female Wistar rats were studied. The magnetism of tumors, liver and heart was determined using Superconductive Quantum Interference Device (SQUID) - magnetometry in a non-contact (13 mm over the tumor) way using specially designed computer programs. In a group of the experimental animals, a ferromagnetic nanocomposite (Ferroplat) was administered as a single intravenous injection and biomagnetism was assessed in 1 h. RESULTS: The magnetic signals coming from Dox-resistant Walker-256 carcinosarcoma in the exponential growth phase were significantly higher in comparison with sensitive tumor. Intravenous administration of Ferroplat increased biomagnetism by at least an order of magnitude, especially in resistant tumors. At the same time, the magnetic signals of the liver and heart were within the magnetic noise. CONCLUSION: The use of SQUID-magnetometry with ferromagnetic nanoparticles as a contrast agent is a promising approach for visualization of malignant neoplasms with varying sensitivity to chemotherapy.

Can SARS-CoV-2 change individual radiation sensitivity of the patients recovered from COVID-19? (experimental and theoretical background).

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Science of Ukraine has been studying the mechanisms and specificities of individual radiation sensitivity (IRS) formation in professionals who work in the field of ionizing radiation, cancer patients and representatives of other population groups. Our data based on the use of G2-test in in vitro irradiated blood lymphocytes in late G2-period of cell cycle indicated an increased carcinogenic risk in professionals with high IRS. We suggest that the COVID-19 pandemic could make significant adjustments in the formation of IRS in professionals who have survived the disease and continue to work with ionizing radiation (IR). Increased systemic inflammatory activity, which persists for a long time in COVID-19 patients, in combination with low-dose range irradiation (professionals who continue to work with IR) and with local irradiation in the high-dose range (radiation therapy for cancer patients) may affect IRS. Repeated determination of IRS in professionals who have had COVID-19 infection, using chromosomal G2-radiation sensitivity assay will answer the question: can SARS-CoV-2 coronavirus affect the IRS? The proposed hypothesis of the radiosensitivity evolution needs further experimental validation using a set of radiobiological indices to clarify the mechanism of IRS formation following COVID-19 infection. The detected changes (increase) of human IRS after COVID-19 must be taken into account for personalized planning of radiotherapy of COVID-19 cancer patients.

Influence of bacterial lectin on key regulatory links of functional activity of macrophages in mice with Ehrlich carcinoma.

BACKGROUND: Recent studies have shown the potential of using different approaches for immunotherapy in cancer treatment. Macrophages (Mph) are one of the promising targets for immunotherapy. AIM: To investigate changes in the functional activity of Mph in mice with Ehrlich carcinoma by nitric oxide (NO)/arginase (Arg), IRF4/IRF5 and STAT1/STAT6 ratios caused by administration of lectin from B. subtilis IMV-7724. MATERIALS AND METHODS: From the 2nd day after Ehrlich carcinoma inoculation into female Balb/c mice, lectin from B. subtilis IMV B-7724 (0.02 mg/mouse) was administered for 10 days. The peritoneal Mph were isolated on days 14, 21, and 28 after tumor transplantation and their functional state (NO production, Arg activity and cytotoxic activity) was examined. The levels of mRNA expression of transcription factors STAT-1, STAT-6, IRF5, IRF4 were evaluated. RESULTS: In lectin-treated animals with Ehrlich carcinoma, the functional state of Mph (NO/Arg ratio, index of cytotoxic activity) was maintained at the level of intact mice exceeding the values in untreated animals with Ehrlich carcinoma at late terms of tumor growth (21, 28 days). Analysis of mRNA expression levels of transcription factors in these animals showed a significant increase (p < 0.05) in the ratio of STAT1/STAT6 on the day 21 and IRF5/IRF4 on day 28 of tumor growth compared to that in untreated mice. CONCLUSIONS: Administration of lectin from B. subtilis IMV B-7724 to mice with Ehrlich carcinoma led to the prevalence of Mph exhibiting the functional properties of M1 type at late-term tumor growth. The transcription factors of the STAT and IRF signaling pathways are involved in the process of Mph polarization induced by lectin from B. subtilis IMV B-7724.

Macrophage polarization in dynamics of Lewis lung carcinoma growth and metastasis.

AIM: To assess the functional state of macrophages based on various manifestations of their activity at the different stages of metastatic tumor growth in C57Bl mice. MATERIALS AND METHODS: On days 7, 14, 21 and 28 after Lewis lung carcinoma transplantation to C57Bl mice, macrophages from various anatomic sites were isolated and tested on their cytotoxicity, metabolic activity, NO production and arginase activity. RESULTS: In the populations of peritoneal and splenic macrophages, on days 7 and 21 of tumor growth antitumor (M1) cells prevailed while on days 14 and 28 tumor-promoting (M2) macrophages predominated. In the population of lung macrophages, cells with M1 phenotype were in the majority in the early stages of tumor growth. On days 21 and 28, M1 cells were gradually substituted by cells exhibiting M2 phenotype. This shift correlated with metastasis to lungs. CONCLUSION: Lewis lung carcinoma growth is accompanied by the gradual change in macrophage polarization from antitumor (M1) towards tumor-promoting (M2) type. These changes were more evident in population of lung macrophages and correlated with the parameters of metastasis.

Modern views on the role of main components of stroma and tumor microinvironment in invasion, migration and metastasis.

The review presents modern ideas about tumor microenvironment, which most researchers recognize as the main "player" in tumor cell invasion, cell migration and metastasis. The current data on the main components of the stroma and the microenvironment, which play the role of the driving force in tumor progression, are analyzed. In particular, the review highlights the issues of origin, biological traits, phenotypic plasticity, functional heterogeneity of activated fibroblasts - myofibroblasts and tumor-associated fibroblasts, which in recent years have received much attention. Such components of the extracellular matrix proteome as collagen and matrix metalloproteinases are discussed in detail. They are mostly produced by activated fibroblasts and, on the one hand, initiate the development of desmoplasia due to type I collagen and, on the other hand, promote degradation of extracellular matrix proteins due to metalloproteinases, which generally leads to tissue remodeling that promotes tumor progression. Possibilities of using the most important indicators of extracellular matrix remodeling as potential markers and targets of clinical strategy are discussed.

Biomagnetism of tumor in rats with Guerin's carcinoma after injection of ferromagnetic nanocomposite (Ferroplat): contactless measurement.

AIM: In order to develop fundamentally new technologies for non-invasive and safer diagnosis of cancer, we aimed to detect non-contact magnetic signals from a malignant tumor in animals treated or not-treated with the ferromagnetic nanocomposite Ferroplat. MATERIALS AND METHODS: Guerin's carcinoma was used as a model of tumor growth. The biomagnetism of the tumor was evaluated in the dynamics of its growth. Ten days after tumor transplantation, Ferroplat was administered intravenously to half of the animals with the tumor and to half of the control animals. The magnitude of the magnetic signals was determined 1 h and every two days after administration of the nanocomposite using a Superconducting Quantum Interference Device magnetometer of the original design. RESULTS: We have found that the magnetic signals coming from the tumor are significantly higher compared to control tumor-free animals. Intravenous administration of a ferromagnetic nanocomposite (Ferroplat: Fe3O4 + cisplatinum) led to a significant increase of the magnetic signal, especially in the tumor tissue, and inhibition of Guerin's carcinoma growth. Ferromagnetic nanoparticles (32.7 nm) are retained in malignant cells for a longer time than in normal ones. CONCLUSION: Tumor cells accumulate iron nanoparticles more intensively than normal ones. Nanocomposite Ferroplat can be used for a targeted delivery of cisplatin to malignant cells.

Association of circulating miR-21, -205, and -182 with response of luminal breast cancers to neoadjuvant FAC and AC treatment.

AIM: To identify the association of serum miRNAs with neoadjuvant polychemotherapy response in patients with breast cancer of luminal A and B subtypes. MATERIALS AND METHODS: We analyzed the expression levels of circulating miR-21, -155, -182, -373, -199a, -205, -375 in serum of 182 breast cancer patients using real-time polymerase chain reaction. Each case was characterized by TMN criteria using morphological and immunohistochemical analyses. RESULTS: Serum levels of miR-205 and -375 are associated with the response of luminal A tumors and miR-205 and -21 with the response of luminal B tumors to neoadjuvant polychemotherapy in fluorouracil + doxorubicin + cyclophosphamide and doxorubicin + cyclophosphamide regimens. In addition, we found correlation of miR-155, -182, -199a, -375 with 3-year relapse-free survival of patients. Based on the obtained data, we developed innovative prognostic and predictive panels to assess the drug sensitivity of tumors and lower the risk of breast cancer recurrence, which would significantly improve the treatment outcomes and the quality of life of patients. CONCLUSIONS: Serum levels of miR-155, -182, -199a, -205, -375 can be used as predictive and prognostic panel for monitoring BC course in Ukrainian population.

NANOG as prognostic factor of prostate cancer course.

The variability of the clinical course of prostate cancer (PC) indicates the need to find factors that could predict the aggressive potential of neoplasms accounting the biological characteristics of tumor cells. In this context, the role of NANOG, a transcription factor involved in maintaining pluripotency and one of the markers of cancer stem cells (CSCs), is being actively studied today. AIM: To investigate the level of NANOG mRNA in tumor tissue of patients with PC and to analyze the possibility of its use as a marker of the disease course. MATERIALS AND METHODS: The study involved 85 patients with PC of stages II-IV. Morphological and immunohistochemical studies were performed on serial paraffin sections of resected PC using monoclonal antibodies to Ki-67 and androgen receptor. NANOG and miR-214 mRNA expression in tumor cells was analyzed by real-time reverse transcription polymerase chain reaction. The identification of CSCs was performed by double-labeled immunohistochemical method using primary antibodies to CD24 and CD44. RESULTS: We have revealed notable variability of NANOG mRNA levels in tumor tissue of patients with PC (mean 4.18 ± 0.65 a.u. with individual deviations from 0.11 ± 0.03 a.u. to 15.24 ± 0.36 a.u.). According to NANOG mRNA levels, two groups of the PC patients were delineated: group 1 and group 2, with the average NANOG mRNA levels of 2.12 ± 0.16 a.u., and 8.68 ± 1.24 a.u., respectively. The NANOG mRNA levels in tumor tissue of PC patients of groups 1 and 2 correlated with preoperative serum prostate-specific antigen level (r = 0.58; p < 0.05 and r = 0.64; p < 0.05, respectively), tumor volume (r = 0.42; p < 0.05 and r = 0.72; p < 0.05, respectively), regional lymph node metastases (r = 0.70; p < 0.05 and r = 0.75; p < 0.05, respectively). High NANOG mRNA levels in tumor cells were associated with such molecular and biological features of PC as androgen receptor expression (r = 0.52; p < 0.05), high proliferative activity (r = 0.60; p < 0.05) and the presence of CSC markers (r = 0.75; p < 0.05). CONCLUSIONS: The findings indicate that NANOG is involved in the formation of the PC malignancy and should be further studied as a potential marker for the prediction of the disease course.

Human microbiota and effectiveness of cancer chemotherapy.

This review presents up-to-date information on the effects of microbiota on the individual chemotherapy sensitivity in cancer treatment. Recent studies have shown that a fine balance between the intestinal microbiota and the immune system is crucial for maintaining an efficacy of cancer chemotherapy. A number of antitumor drugs have complex mechanisms of action involving not only direct effects but also the activity of the intestinal microbiota and the immune system. A unique combination of these factors contributes to the individual chemotherapy sensitivity.

Macrophages - a perspective target for antineoplastic immunotherapy.

The review discusses the data on the functional/phenotypic M1/M2 types of macrophages and their chimeric forms, the molecular mechanisms of polarization of these cells, and their role in the development of malignant tumors. Information on the prognostic value of the presence (density and location) of M1/M2 cells in tumor tissue is analyzed. Our own results evidence on the necessity of determination of the functional/phenotypic state of M1/M2 macrophages from different biological niches in the dynamics of tumor growth, in particular in terms of NO level and arginase activity.

Tumor microenvironment-derived miRNAs as prognostic markers of breast cancer.

AIM: To study expression of miRNA derived from tumor microenvironment in patients with breast cancer (BC) as the aspect of tumor-host interaction. MATERIALS AND METHODS: The expression levels of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2/neu) were analyzed in tissue of BC using immunohistochemical method. Relative expression levels of the miR-155, -320a, and -205 were examined in tissue and sera from BC patients using quantitative reverse transcription polymerase chain reaction. RESULTS: Serum and tissue miR-155, -320a, and -205 levels in patients with BC are of low diagnostic value as such for differentiation of malignant and non-malignant breast neoplasms. Nevertheless, we established the relation of circulating and tissue miR-155, -320a, and -205 to lymph node metastases and basal breast cancer subtype. CONCLUSIONS: Changes of miR-155, -320a, and -205 expression in tumor tissue and sera of BC patients provide information about major clinical-pathological characteristics of BC.

MicroRNAs are a key factor in the globalization of tumor-host relationships.

A new round of molecular oncology development in the post-genomic era significantly changes the conventional understanding of the nature and origin of the malignant process. Increasingly, fundamental phenomena are emerging that change the "canonical" views of the dominant role of gene mutations that contribute to the uncontrolled proliferation and emergence of heterogeneous malignant cells. Recent numerous studies have shown that significant variability in the initiation, proliferation and control of the apoptotic program of tumor cells is due to numerous epigenetic processes, including the level of expression of microRNAs (miRNAs). This paper reviews the literature data and presents the results of own research in which miRNAs have been found to form a molecular phenotype for malignancy. Their role as a "conductor" of the functioning of a genetic-epigenetic orchestra that coordinates various aspects of malignancy has been suggested. MiRNAs have been shown to be an active participant in balancing mechanisms in the development of controversial processes in breast cancer cell lines of varying degrees of malignancy. The analysis of the literature data and the own studies of the expression profile of only a few miRNAs suggests that scientists and clinicians have received a new marker and a target that simultaneously plays the role of an active insider in both the oncogene-oncosuppressor relationship and in the globalization of this process at the tumor-host level. Further investigation of the "alarm" marker in this network will allow to reconsider the molecular genetic classification of neoplastic disease, which will provide the development of a new strategy for cancer therapy.

The influence of lactoferrin on elemental homeostasis and activity of metal-containing enzymes in rats with Walker-256 carcinosarcoma.

AIM: To investigate the content of essential elements (EE): copper, zinc, magnesium, iron and calcium and the evaluation of the activity of metal-containing enzymes - ceruloplasmin (CP), myeloperoxidase (MPO) and the content of transferrin (TF) in blood plasma (BP) and tumor tissue (TT) of animals with Walker-256 carcinosarcoma treated with lactoferrin (LF). MATERIALS AND METHODS: The study of the EE content and the activity of the abovementioned enzymes was carried out on rats with Walker-256 carcinosarcoma treated with LF at the doses of 1 and 10 mg/kg of body weight. The quantitative content of EE in BP and TT of animals was determined using the inductively coupled plasma atomic emission spectroscopy (ICP-AES). Determination of CP activity, content of TF and hemochromes was performed using the method of electron paramagnetic resonance (EPR), and MPO - by unified biochemical method. RESULTS: The introduction of LF at the doses of 1 and 10 mg/kg resulted in a decrease in the ratio of Cu/Zn in BP and even more expressed decrease of Ca/Mg ratio in TT. Administration of LF, especially at a dose of 10 mg/kg, affected the increase in CP and MPO activity in BP. It has been shown that administration of LF at a dose of 10 mg/kg led to an increase in oxidative products of destruction of the hemoglobin-hemochrom system in the TT, against the background of lowering the TF content. CONCLUSIONS: The administration of LF, especially at a dose of 10 mg/kg, led to metabolic alterations associated with inhibition of the tumor process. The detected modulating effect of LF on the content of the EE and the activity of the CP and MPO may be a basis for correction of the elemental balance in carcinogenesis.

Overexpression of the mitochondrial ribosomal protein S18-2 in the invasive breast carcinomas.

BACKGROUND: Recent studies allow to consider the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) as a potential oncoprotein, which suggests the need for further characterization of its expression in tumors of different genesis including breast cancer (BC). The aim of the study was to analyze the expression of the S18-2 protein in BC of luminal A and basal subtypes. MATERIALS AND METHODS: Operational material of BC patients stage І-ІІ (luminal A subtype, n = 30, and basal subtype, n = 10) was studied with the use of morphological, immunohistochemical, statistical and bioinformatic methods. RESULTS: Using the immunohistochemical analysis, we found that the S18-2 protein showed the nuclear signal in 66.7% of luminal A subtype BC samples and 80.0% of basal subtype BC samples. The variability of the S18-2 expression in both the luminal A and basal subtypes of BC was revealed. Noteworthy, the number of cells expressing S18-2 in high-proliferating tumors of luminal A and basal subtype is significantly higher than in tumors with a low proliferative potential (p < 0.05). In 10 samples of luminal A subtype, the nuclear S18-2 signal was higher than median value. Moreover, the S18-2 protein was overexpressed in 4 out of such 10 samples. Metastases in the lymph nodes were found in 3 out of 4 patients with the stage II BC, low differentiation grade of the tumor and high proliferative activity. The bioinformatic analysis confirms our preliminary findings that the trend for increasing expression of the S18-2 protein in tumors correlates with the aggressiveness of malignant BC. CONCLUSION: The S18-2 protein may be a marker of cancer aggressiveness in BC patients.

Influence of ferromagnetic nanocomposite (Ferroplat) on human breast cancer cells of different malignancy degrees: pro/antioxidant balance and energy metabolism.

AIM: To study the effect of Ferroplat (FrP) on the indexes of pro/antioxidant balance and energy metabolism in breast cancer cells of different malignancy degree and different sensitivity to drug therapy. MATERIALS AND METHODS: The study was carried out on breast cancer cells of low (T47D, MCF-7) and high malignancy degree (MCF-7/DDP (cisplatin-resistant), MDA-MB-231, MDA-MB-468) using cell culture techniques, immunocytochemical, biochemical, biophysical methods, flow cytometry and polarography. RESULTS: We established that the addition of FrP to the culture medium reduces the activity of glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and the level of non-protein thiols by 32-41% (p < 0.05). At the same time, there was an increase of the total level of ROS and the rate of NO generation by inducible NO synthase by 1.7-2.5 times (p < 0.05). This testifies that FrP disturbs the antioxidant balance in cells, resulting in their death. Also, the use of FrP led to a decrease in the rate of oxygen absorption in MCF-7 and T47D cells by 26% and 25%, respectively (p < 0.05). In cells of high malignancy degree this index decreased by 38-40% under the influence of FrP. Incubation of MCF-7 and T47D cells with the indicated agent also reduced the content of phospholipid cardiolipin by 15-16% (p < 0.05), and in MDA-MB-231, MCF-7/DDP, MDA-MB-468 cells - by 29%, 30% and 32%, respectively. In addition, the effect of FrP caused a decrease in the levels of Mg2+ and lactate in MCF-7 and T47D cells by 21-29% and 14-24%, respectively, whereas in MDA-MB-231, MDA-MB-468, MCF-7/DDP cells - by 34-38% and 32-35%, respectively. In this case, the agent raised the level of glucose in the cells of low malignancy degree by 20-23% (p < 0.05), and in the cells of high malignancy degree and with the phenotype of drug resistance - by 31-36%. However, the nanocomposite did not affect the activity of lactate dehydrogenase in all studied breast cancer cells. CONCLUSION: The study has shown that FrP has an effect on the pro/antioxidant balance and energy metabolism of cancer cells. In addition, the denoted effect of FrP was more pronounced in the breast cancer cells with a high malignancy degree and the phenotype of drug resistance.

Antitumor and genotoxic effects of lactoferrin in Walker-256 tumor-bearing rats.

AIM: To investigate the influence of exogenous lactoferrin (LF) on tumor growth, energy and lipid metabolism of Walker-256 carcinosarcoma and to assess genotoxic effects of LF. MATERIALS AND METHODS: The study was performed on Walker-256 tumor-bearing rats. Total lipids and phospholipids were determined by thin-layer chromatography. Comet assay was used to investigate the genotoxic effects of LF. RESULTS: Daily i.p. administrations of exogenous LF at concentrations of 1 mg/kg and 10 mg/kg starting from the 4th day after tumor transplantation suppressed growth of Walker-256 carcinosarcoma by almost 44%. After treatment with recombinant LF in both doses, the phospholipid composition of Walker-256 carcinosarcoma cells was changed (3-fold increase of phosphatidylethanolamine, 3.4-fold increase of phosphatidylcholine, and 1.8-fold increase of sphingomyelin, while the cardiolipin content decreased by 67%. Exogenous LF was not genotoxic for bone marrow cells (as assessed by the ratio of PCE/NCE, number of micronuclei) and peripheral blood lymphocytes (percentage of DNA in the tail of a comet) in Walker-256 carcinosarcoma-bearing rats. CONCLUSION: Exogenous LF caused the inhibition of Walker-256 carcinosarcoma growth and a decrease in the microviscosity of plasma cell membranes, and exerted no genotoxicity toward bone marrow cells and peripheral blood of experimental animals.

Analysis of the survival of patients with breast cancer depending on age, molecular subtype of tumor and metabolic syndrome.

AIM: To analyze the survival of patients with breast cancer (BC) depending on age, molecular subtype of the tumor and the presence of metabolic syndrome. PATIENTS AND METHODS: We have analyzed the results of examination and treatment of 202 patients with BC of stages I-III. The patients were distributed by age into 2 groups. The group 1 included 86 elderly patients (from 65 to 84 years old), the group 2 - 116 younger patients (from 32 to 64 years). An overall 1-, 3- and 5-year survival rates of the treated patients were assessed. The significance of factors influencing the overall survival (OS) of patients with BC was determined using the methods of statistical analysis. RESULTS: Molecular subtype of BC significantly affects survival rates: in a case of a luminal B subtype the 5-year OS was 71.6 vs 80% (p < 0.05) in groups 1 and 2, respectively while in a case of a basal-like subtype it was 60.2% and 71.6% (p < 0.05). The presence of metabolic syndrome significantly reduced the 5-year OS (up to 70.7% and 80.6%, p < 0.05 in groups 1 and 2, respectively). CONCLUSION: The OS is lower in elderly patients with BC compared with younger patients, especially in those who suffer from metabolic syndrome.

Effects of exogenous lactoferrin on phenotypic profile and invasiveness of human prostate cancer cells (DU145 and LNCaP) in vitro.

AIM: To investigate the biological effects of exogenous lactoferrin (LF) on phenotypic profile and invasiveness of human prostate cancer (PC) cells in vitro. MATERIALS AND METHODS: Human PC cell lines (LNCaP, DU-145) were cultured with an exogenous LF at a dose corresponding to IC30. The expression levels of steroid hormone receptors (androgen receptor, estrogen receptor, progesterone receptor), Her2/neu, Ki-67, E- and N-cadherin, were monitored by immunohistochemical analysis. The levels of miRNAs were assessed using q-PCR. The invasive activity of the cells was examined in a standard invasion test. RESULTS: Exogenous LF reduced expression of steroid hormone receptors (ERα and PR) and Ki-67 in both PC cell lines. The expression of E-cadherin increased significantly in LF-treated DU-145 cells. Also, we established the decrease in invasive activity upon LF treatment by 40% and 30% in DU-145 and LNCaP cells, respectively. In DU-145 cells, incubation with exogenous LF resulted in an increase in the expression of oncosuppressive (miR-133a and miR-200b) miRNAs. CONCLUSIONS: Exogenous LF causes the changes in phenotypic characteristics of PC cells and levels of oncogenic and oncosuppressive miRNAs involved in the regulation of key cellular processes.