RESUMEN
Excessive production of reactive oxygen species is the main cause of hepatocellular carcinoma (HCC) initiation and progression. Water-soluble pristine C60 fullerene is a powerful and non-toxic antioxidant, therefore, its effect under rat HCC model and its possible mechanisms were aimed to be discovered. Studies on HepG2 cells (human HCC) demonstrated C60 fullerene ability to inhibit cell growth (IC50 = 108.2 µmol), to induce apoptosis, to downregulate glucose-6-phosphate dehydrogenase, to upregulate vimentin and p53 expression and to alter HepG2 redox state. If applied to animals experienced HCC in dose of 0.25 mg/kg per day starting at liver cirrhosis stage, C60 fullerene improved post-treatment survival similar to reference 5-fluorouracil (31 and 30 compared to 17 weeks) and inhibited metastasis unlike the latter. Furthermore, C60 fullerene substantially attenuated liver injury and fibrosis, decreased liver enzymes, and normalized bilirubin and redox markers (elevated by 1.7-7.7 times under HCC). Thus, C60 fullerene ability to inhibit HepG2 cell growth and HCC development and metastasis and to improve animal survival was concluded. C60 fullerene cytostatic action might be realized through apoptosis induction and glucose-6-phosphate dehydrogenase downregulation in addition to its antioxidant activity.
RESUMEN
BACKGROUND: Cancer stem cells (CSCs) provide self-renewal of the tumor after radiation and chemotherapy. These cells are important during tumor development. The in vitro model of avascular tumor that enriched of cells with stem like characteristics is critical to understanding of the role CSCs in the tumor. METHODS: Cell viability was evaluated by MTT assay. The expression of cancer stem cells markers (CD133, CD44, CD24 and bmi-1) in 2D cell culture and multicellular tumor spheroids (MCTS) of MCF-7 cells was evaluated. The Stemi2000 software AxioVisionRed 4.7 was used for image processing. The volume of spheroids was calculated by Bjerkvig formula. RESULTS: The highest expression of CD133, CD44, CD24 and bmi-1 receptors was detected in MCTS, enriched with cancer stem cells (eMCTS). Cell aggregates of eMCTS culture were returned from suspension to adhesive conditions. It was found that the cells of the MCTS surface layers were enriched with CD133, CD44, CD24, bmi-1, EpCAM, vim markers, but not adherent cells. eMCTS are less sensitive to anticancer drugs (cisplatin, methotrexate and doxorubicin), than adhesive cell culture and MCTS cultured under standard conditions in a complete nutrient medium (P<0.05). CONCLUSIONS: We observed that eMCTS population possesses aggressive phenotypic characteristics such as invasion, cancer stem cell markers and chemoresistance. eMCTS model could improve the screening efficiency of therapeutical agents against CSCs.
RESUMEN
The effect of IFNα-2b on the migration, proliferation, and expression of epithelial and mesenchymal markers of MCF-7 tumor adenocarcinoma cells in 2D and 3D cell cultures was examined. A significant cytostatic effect of IFNα-2b on the tumor population was detected. It was found that changes in the expression of epithelial (CKs and EpCAM) and mesenchymal markers were caused by changing the growth type of the tumor population. IFNα-2b inhibited migration of tumor cells to the suspension fraction and promoted an increase in expression of CK and EpCAM in 2D and 3D cell cultures, but only in the 3D culture was expression of vimentin increased. IFNα-2b caused an increase in CK and EpCAM expression by 50.5% and 47.8%, respectively, compared with the control in the 2D cell culture. In the 3D cell culture this increase was 33% and 34%, respectively, compared with the control. IFNα-2b stimulated the differentiation and inhibited the migrational ability of tumor cells in the early stages of breast cancer development.
