e15077 Background: Plant metabolites are traditionally a valuable source of anticancer drugs. The huge variety of molecular structures found in plants makes it possible to isolate substances that possess not only antimitotic, but also anti-migratory properties on cancer cells. The objective of this study was to evaluate the anti-migratory activity of selected metabolites from Petasítes sp. plants. Methods: Cells of cancer cell cultures PC3 (prostate cancer), A431 (skin cancer), CaCo-2 (colorectal cancer), HeLa (cervical cancer) and T98G (glioma) were seeded in an amount of 15*104 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion the test substances at a concentration of 40 µM were added, and a wound healing assay was performed according to the standard procedure. The study included the following metabolites: 1) substance 1 (S1) - 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one; 2) substance 2 (S2) - 5-(hydroxymethyl)furan-2-carbaldehyde; 3) substance 3 (S3) - corynan. The wound area was measured using a Lionheart FX imager (BioTek, USA) at starting time point and after 48 hours of cultivation. Data are presented as mean±95% confidence interval (n = 12). Results: The studied cultures were found to be differently sensitive to the tested substances. Cells of CaCo-2 and PC3 cultures did not demonstrate a significant decrease in mobility, as the degree of scratch overgrowth did not decrease compared to the control without the addition of substances (α = 0.05, df = 22) in all variants of the experiment. However, the A431 skin cancer culture showed reduced motility in all three trials compared to the no-substance control. Namely, the wound area reduction was 81.52 ± 9.6% in the control, 63.77 ± 8.4% in S1 variant, 62.42 ± 6.3% in S2 variant, and 12.05 ± 7.1% in S3 variant. Also, a slowdown in cell motility was observed in HeLa (28.92±5.1% compared to 37.0±6.3% in control) and T98G cells (82.41±9.1% compared to with 97.35±1.9% in control) when incubated with S1. Taking into account the correction for multiple comparisons, only the results for A431 turned out to be significant, but the results obtained for HeLa and T98G cultures were not significant at a corrected significance level (α = 0.003, df = 22). Conclusions: Further studies of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one anti-migratory properties are of particular interest, since it showed promising results in three of the five studied cancer cell cultures.
e15079 Background: Initially, berberine was used as an antimicrobial agent in traditional medicine, but its anticancer properties were later discovered. In addition to its cytotoxic effect, berberine also has the ability to inhibit cell motility, which has been demonstrated in some permanent cancer cell lines. The objective of this study was to assess berberine anti-migratory activity in permanent cell cultures compared to primary cell cultures which are generally thought to better reflect tumor characteristics. Methods: H1299 lung cancer, PC3 prostate cancer, and T98G glioma cells, as well as primary cell cultures of the corresponding cancer obtained in our laboratory, were planted in an amount of 15*104 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion berberine was added in concentration 5 µM, and a wound healing assay was performed according to the standard procedure. Cell plates were continuously incubated and photographed in Lionheart FX imager (BioTek, USA) at 37°C and 5.0% CO2. The extent of cell migration was measured as the percentage reduction in wound area after 48 hours of incubation relative to baseline. Data are presented as Mean ± 95% confidence interval (n = 12). Results: The use of berberine at a concentration of 5 µM led to a significant decrease in cell motility in permanent cultures of lung cancer, glioma and prostate cancer. Namely, the reduction in the wound area after 48 hours of incubation with bereberine was 74.52±12.3% (compared with 94.56±6.2% in the control) in H1299 cell culture, 38.22±10.6% (compared with 83.89±15.5% in the control) in T98G cell culture, and 48.6±7.5% (compared with 69.56±8.1% in the control) in PC3 cell culture. The resulting difference between the control and experimental groups in permanent cell cultures was statistically significant at a significance level of 5% (df = 22). At the same time, the values of wound area reduction for primary cultures of the same cancers did not differ significantly in the control and under the influence of 5 μM berberine at the accepted level of significance. Namely, the reduction in the wound area after 48 hours of incubation with bereberine was 84.79±11.2% (compared with 81.47±15.3% in the control) in lung cancer primary cell culture, 94.64±5.1% (compared with 91.73±6.8% in the control) in glioma primary culture, and 62.63±5.8% (compared with 61.1±8.9% in the control) in prostate cancer primary cell culture. Conclusions: Permanent cell lines are more sensitive to berberine anti-migratory activity than primary cancer cell lines of the same localization.
e15003 Background: Taxanes and platinum compounds are widely used in cervical cancer chemotherapy. In particular, a combination of 75 mg/m2cisplatin and 175 mg/m2 paclitaxel, which suggests a doses ratio of 1:2.3, is recommended as first-line systemic chemotherapy. Although this combination has performed well in clinical practice, little is known about its effect on cervical cancer cell biology in vitro. This study assessed the effect of combined application of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa cells. Methods: HeLa cells were seeded at 3000 cells per well in a 96-well plate (Eppendorf, Germany) and incubated for 24 hours in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37°C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing chemotherapy drugs in combination or as standalone agents in a series of two-fold dilutions: 0.03 - 32 µg/mL cisplatin and 0.07 - 73.6 µg/mL paclitaxel. After 2 h exposition to studied compounds the medium was replaced and cells were incubated for another 72 hours. At the end of the experiment, the number of living cells was assessed using the MTT test. Viability was determined as the number of living cells in % of the control without the addition of chemotherapy drugs. Results: The combination of cisplatin with paclitaxel demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 μg/ml to 8 μg/ml. The difference between the mean viability values for each concentration between pure cisplatin and its 1:2.3 mixture with paclitaxel was significant at α = 0.05 (df = 14). The decrease in viability is especially dramatic at non-toxic concentrations of cisplatin (0.03 - 0.5 μg/ml) and is about 60% over this concentration range. However, when moving to toxic concentrations of cisplatin (0.5-32 μg/ml), the difference in the viability of HeLa cells between pure cisplatin and its combination with paclitaxel linearly decreases with increasing cisplatin concentration, becoming insignificant in the range of 8-32 µg/ml. However, when comparing the dose-response curves for pure paclitaxel and its combination with cisplatin, we see a significant reduction in cytotoxic activity compared with pure paclitaxel. The difference in cell viability reaches its maximum (45%) at a paclitaxel concentration of 2.3 µg/ml and is significant at α = 0.05 (df = 14). Conclusions: The combined use of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa culture has a greater cytotoxic activity compared to pure cisplatin. However, compared with pure paclitaxel, the effectiveness of its combination with cisplatin is significantly lower, which indicates the antagonism of the two substances.
e15009 Background: Multiple myeloma (MM) is a B-cell malignancy resulting from the abnormal proliferation of neoplastic plasma cells that produce monoclonal immunoglobulin (Ig). The high variability of the course of this disease, its genetic clonal heterogeneity, is due to chromosomal deletions, chromosomal hyperploidy involving an odd number of chromosomes, as well as genetic aberrations, such as rearrangement of the Ig heavy chain gene loci. Since the available biomarkers do not take into account this feature of MM, there is a need to develop more advanced biomarkers that will more accurately predict the course of the disease and response to treatment. Methods: The collection of MM samples included biological samples obtained from patients over 18 years of age with a diagnosis of MM, who received treatment in the National Medical Research Center of Oncology since 2019. Only patients who signed an informed consent for the use of their biomaterial for scientific purposes were included in the project. The material was collected according to the developed algorithm of clinical information and biological material collection, sample preparation, quality control and storage in the cryostorage of the National Medical Research Centre for Oncology of the Ministry of Health of Russia (Rostov-on-Don). Results: As of December 23, 2021, collection consists of 387 samples of whole blood, serum, plasma and mononuclear cells obtained from 42 MM patients of both sexes, whose average age was 59.7 ± 1.49 (±SD) years. Each patient was assigned a unique identification number. Freezing of the obtained samples occurred in accordance with the low-temperature storage protocol. Registration, accounting and certification of the material were carried out in a specialized database for recording and storing information about biological samples. Conclusions: The identification of MM biomarkers is important for increasing the sensitivity of molecular monitoring, which makes it possible to stratify patients into risk groups for early relapses and treatment resistance development. Thanks to the accumulated experience, the Biobank of the National Medical Research Centre for Oncology of the Ministry of Health of Russia serves as a valuable resource for providing research in the development of new predictive molecular markers.
e15002 Background: Bleomycin is a glycopeptide antibiotic with anticancer properties. Clinical data indicate a relatively low efficacy of bleomycin in mono regimen, which is also accompanied by side effects from high doses. That’s why so it is more often used in relatively low doses in combination with other chemotherapy drugs. In particular, in cervical cancer, bleomycin is used in combination with cisplatin in a dose ratio of 0.8:1. Despite good clinical results, it is not known how the two drugs interact in vitro. The aim of this study was to evaluate the effect of combined application of bleomycin and cisplatin on HeLa cells. Methods: HeLa cells were seeded at 3000 cells per well in a 96-well plate (Eppendorf, Germany) and incubated for 24 hours in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37°C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing chemotherapy drugs in combination or as standalone agents in a series of two-fold dilutions: 0.03 - 32 µg/mL cisplatin and 0.012 – 12.8 µg/mL bleomycin. After 2 h exposition to studied compounds the medium was replaced and cells were incubated for another 72 hours. At the end of the experiment, the number of living cells was assessed using the MTT test. Viability was determined as the number of living cells in % of the control without the addition of chemotherapy drugs. Results: The combination of cisplatin with bleomycin demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 µg/ml to 8 µg/ml, and pure bleomycin in the range of 0.012 - 12.8 µg/ml. The difference between the mean viability values for each concentration of pure bleomycin or pure cisplatin and their 0.8:1 mixture was significant at α = 0.05 (df = 14). Observed decrease in the viability of HeLa cells in comparison with pure substances is most pronounced in the range of non-toxic concentrations for both substances in mono regimen, namely 0.03 - 0.5 μg/ml for cisplatin, and at concentrations less than 0.125 μg/ml for bleomycin. Here, the increase in the difference between the dose-response curves grows as the concentration of the studied drugs increases. At cisplatin concentrations of 0.5–32 μg/ml, the difference in HeLa cell viability between pure cisplatin and its combination with bleomycin, on the contrary, decreases linearly with increasing cisplatin concentration, becoming insignificant above 16 μg/ml. Conclusions: The combined use of bleomycin and cisplatin on HeLa culture in a dose ratio of 0.8:1 exhibits synergistic properties that are most pronounced in the concentration ranges of both substances that do not have a cytotoxic effect in mono regimen.
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