ABSTRACT
OBJECTIVE To explore downstream regulatory pathway of microRNA-21 (miR-21) in colon cancer cells (RKO) through detecting miR-21 and its target PDCD4, and the influence of miR-21 regulation on the sensitivity of RKO cells to 5-fluorouracil (5-FU). METHODS 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the effect of 5-FU on the viability of RKO cells with knockout of miR-21 or high expression of PDCD4. Real-time was used to determine the expression of PDCD4, ABCC5 and CD44 in RKO cell after knockout of miR-21. RESULTS MTT assay reveals that the IC50 of 5-FU in RKO-WT cells (52.82 ± 0.06 umol/L) was about 67% higher than in miR-21 knockout cells (32.23 ± 0.05 umol/L) (P < 0.05), and the apoptosis ratio elevated after knockout of miR-21. High expression of PDCD4, a target gene of miR-21, can negatively regulate the expression of ABC transporter ABCC5 and the stem cell marker CD44. CONCLUSION MiR-21 can mediate the drug resistance to 5-FU by inhibiting its target PDCD4, which can regulate the expression of ABCC5 and CD44 genes.
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily G, Member 5 , ATP-Binding Cassette Transporters , Genetics , Antimetabolites, Antineoplastic , Pharmacology , Apoptosis Regulatory Proteins , Physiology , Cell Line, Tumor , Colonic Neoplasms , Drug Therapy , Pathology , Drug Resistance, Neoplasm , Fluorouracil , Pharmacology , Hyaluronan Receptors , Genetics , Lipoproteins , Genetics , MicroRNAs , Physiology , RNA-Binding Proteins , PhysiologyABSTRACT
Electrochemotherapy was instituted for sarcoma, and the tumor inhibitory ratio, curing ratio, vascular endothelial growth factor, microvessel density and mechanism were measured and analyzed. The results indicate that the curing ratio of electrochemotherapy for sarcoma is 84.6%. The present research provides experimental evidence for the security, mechanism and feasibility of electrochemotherapy in clinical practice.
Subject(s)
Animals , Mice , Antineoplastic Agents , Bleomycin , Drug Delivery Systems , Methods , Electrochemotherapy , Methods , Electroporation , Methods , Sarcoma 180 , Therapeutics , Vascular Endothelial Growth Factor AABSTRACT
This is our first time report of S-180 cell handled with various voltages, capacity and pulse number. Many pores on the S-180 cell membrane can be observed under scanning electron microscope. By the stains of trypan blue, we have known the influence of electric parameters on the ratio of poration. The results show that the ratio of electroporation has positive correlation with the voltages and the pulse number while negative correlation with the capacity.
Subject(s)
Animals , Mice , Cell Membrane Permeability , Electromagnetic Fields , Electroporation , Methods , Sarcoma 180 , Tumor Cells, CulturedABSTRACT
In this paper are analyzed the effect of electrochemotherapy and its mechanism. The favorable parameter of electric pulses (EP) was studied in vitro using the S-180 cells exposed to various EP. After the tumor model was copied, the tumor-bearing mice were randomly divided into four groups: control, chemotherapy, electrotherapy, and electrochemotherapy. The tumor inhibitory ratio, the cure ratio and the level of oxygen free radicals (OFR) were determined. The inhibitory ratio and cure ratio of electrochemotherapy group were significantly higher than those in the chemotherapy, electrotherapy and control groups (P < 0.05). The injury of OFR was decreased while the immunological competence was increased. The mechanism of electrochemotherapy may be related with the enhancement of cell membranepermeability, the depression of drug resistance, the improvement of immunological competence, and so on.
Subject(s)
Animals , Mice , Antineoplastic Agents , Bleomycin , Drug Delivery Systems , Methods , Electric Stimulation Therapy , Methods , Electrochemistry , Electroporation , Methods , Random Allocation , Sarcoma 180 , TherapeuticsABSTRACT
This study evaluated the effects of electric pulses combined with antitumor drugs on S180 tumor cells. It was found that the growth of S180 sarcoma was inhibited with a maximum inhibition ratio of 95.5% after the use of electric pulses in combination with the injection of bleomycin (BLM), and the blood vessels of tumor were obviously fewer than those of the untreated tumor in vivo. The mitochondria of S180 tumor cells were swollen after the use of electric pulses in combination with adriamycin. The results showed that electrochemotherapy has evident inhibitory effect on the growth of S180 sarcoma and the mechanism may involve the suppression of tumor angiogenesis and changes in the ultrastructures of tumor cells.
Subject(s)
Animals , Mice , Antimetabolites, Antineoplastic , Bleomycin , Combined Modality Therapy , Electric Stimulation Therapy , Methods , Electrochemistry , Neovascularization, Pathologic , Sarcoma 180 , TherapeuticsABSTRACT
This article reports the experiment studies on treating the S-180 sarcomas of KM mice with high-intensity electric pulse and antitumor drug (cyclophosphamide). The results showed that the experimental group of electric field combined with drug has the best effect on tumor, compared with the control group. In addition, electric field can inhibit the formation of vas Capillaries and decrease the supply of nutrition for tumor cell. In conclusion, electric field has inhibited the growth of tumor.