Amino Acids ; isolation & purification ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Binding Sites ; Colchicine ; pharmacology ; Humans ; Microtubules ; drug effects ; physiology ; Paclitaxel ; pharmacology ; Tubulin ; chemistry ; isolation & purification ; metabolism ; Vinblastine ; pharmacology

This study was purposed to investigate the biological effect of vinblastine (VLS), usually known as inductor of mitotic arrest, on MOLT-4 of ALL cells and to evaluate its significance. The cell arrest in M phase and/or cell apoptosis were induced by treatment of MOLT-4 cells with 0.05 microg/ml VLS for 0 - 12 hours; the DNA histogram was detected by flow cytometry; the morphological changes of cells were observed by confocal microscopy; the cell cycle distribution, cell apoptosis and morphological changes of cells before and after arrest were analyzed by using arrest increasing rate (AIR), arrest efficiency (AE), apoptosis rate (AR) and morphologic parameters respectively. The results indicated that the cell arrest did not accompanied by significant increase of apoptosis rate; the DNA histogram of cell arrest showed dynamic change of cell cycle in time-dependent manner; the arrest efficiency could be quantified. The cell arrest at M phase was accompanied by cell stack in S phase, the cell proliferation rate dropped after cell arrest occurred. The cells arrested at M phase possessed of characteristic morphologic features in cell mitosis. It is concluded that the vinblastine can solely induce arrest of MOLT-4 cells at M phase. This study provides experimental basis for further investigating the relation of cell cycle arrest to apoptosis, mechanism of checkpoint and development of new anticancer drugs.
Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Flow Cytometry ; Humans ; Tumor Cells, Cultured ; Vinblastine ; pharmacology

OBJECTIVETo compare effects of vinblastine (VLB) nanoparticles (NPS) and VLB physiologic saline solution on inhibiting glioma cell lines C6 growth and inducting its apoptosis.

METHODGlioma cell lines C6 were respectively treated with 500 micro x L(-1) VLB NPS and VLB physiologic saline solution for 7 days. Amount of cells were counted by blood cell counting chamber. Glioma C6 growth curve was draw according to cells amount. Clone formation rate of glioma C6 was detected after 500 microg x L(-1) VLB NPS and VLB physiologic saline solution incubation for 2 weeks. In addition, the whole morphology of glioma C6 were observed by inverted microscope and inverted fluorescence microscope after 500 microg x L(-1) VLB NPS and VLB physiologic saline solution incubation for 48 h.

RESULTEntrapment of VLB in NPS may significantly inhibit glioma cells C6 growth from 2 to 7 days compared with VLB physiologic saline solution in the same dose (P < 0.05). Clone formation rate of glioma C6 in VLB physiologic saline solution group is 1. 3 times better than VLB NPS. The difference between VLB NPS and VLB physiologic saline solution is significant (P < 0.05). Results of morphology change indicated glioma cells C6 with the VLB NPS treatment were intermediate or end stage, missed structure integrality. Amount of cells was distinctly decreased, and apoptosis cells number was apparently increased compared with VLB physiologic saline solution group.

CONCLUSIONVLB NPS have stronger cytotoxicity to glioma cells line C6 compared with VLB physiologic saline solution in the same dose. NPS may be effective as promising carrier for the transport of VLB into the glioma cells.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Glioma ; drug therapy ; physiopathology ; Nanoparticles ; chemistry ; Rats ; Vinblastine ; pharmacology

OBJECTIVETo compare antiproliferation effects of vinblastine nanopraticles and vinblastine water solution in human glioma cell lines BT325.

METHODVinblastine nanoparticles were prepared by emulsion polymerization process and using dextran as a stabilizing agent. It was characterized by means of morphology, size, drug entrapment efficiency and loading efficiency. Human glioma cell lines BT325 were treated with different concentrations of vinblastine nanoparticles and vinblastine water solution for 48 h, Antiproliferation effect was measured by MTT method. Morphological changes were observed by inverted microscope, transmission electron microscope and scanning electron microscope.

RESULTMean diameter of VLB-PBCA-NP was about 74.4 nm, and drug entrapment efficiency and loading efficiency was 78.47% and 39.24%, respectively. Cell growth inhibition rate of vinblastine nanoparticles group and vinblastine water solution group in a concentration range (5-5 000 g x L(-1)) for 48 h was 41%, 49%, 73%, 83% and 28%, 33%, 54%, 60% respectively. Entrapment of VLB in NPS may distinctly degrade absorbency as compared to free drugs. Glioma cell BT325 which treated with VLB water solution were initial stage of apoptosis, and apoptosis body were forming. But VLB NPS-treated BT325 cells were intermediate or end stage, and missed structure integrality.

CONCLUSIONVLB-PBCA-NP and VLB water solution could inhibit the growth of human glioma cell lines BT325, and VLB nanoparticles have stronger inhibition effect compared with VLB water solution in the same dose. PBCA may be effective as promising carrier for the transport of vinblastine into the glioma cells.

Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Microscopy, Electron, Transmission ; Nanoparticles ; Vinblastine ; pharmacology

This study was purposed to explore the Rituximab (RTX)-mediated sensitization of B-NHL cell lines to apoptosis induced by Gemcitabine or Navelbine and its possible mechanism. The inhibitory rate of B-NHL cell proliferation was detected by XTT method, the IC₅₀ from Gemcitabine or Navelbine and combination of Gemcitabine or Navelbine with RTX was compared. The expression level of antiapoptotic protein BCL-2 in Daudi, Ramos, Raji and Namalwa cells treated with RTX of 20 μg/ml for 24 hours was detected by Western blot. The results showed that the RTX as a single agent could weakly induce the apoptosis of Daudi, Namalwa, Raji and Ramos lymphoma cell lines, the inhibiting rate of cell proliferation ranged from 3% to 10%; RTX could sensitize significantly the cytotoxity of Gemcitabine or Navelbine in Daudi, Namalwa and Raji cell lines; The expression of BCL-2 in Raji and Namalwa cell lines treated with RTX of 20 microg/ml for 24 hours was down-regulated. It is concluded that RTX can sensitize the cytotoxicity of Gemcitabine or Navelbine to the human lymphoma cell lines which displayed the synergistic effect on Daudi, Namalwa and Raji cell lines. The BCL-2 expression level in Raji and Namalwa cell lines treated by RTX is down-regulated which may be one of the mechanisms sensitizing the cytotoxicity of Gemcitabine or Navelbine.
Antibodies, Monoclonal, Murine-Derived ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; drug effects ; Cytotoxicity, Immunologic ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Humans ; Lymphoma, T-Cell ; Proto-Oncogene Proteins c-bcl-2 ; Rituximab ; Vinblastine ; analogs & derivatives ; pharmacology

OBJECTIVETo evaluate the effects of topical DMSO and intralesional hyaluronidase administration, used alone or in combination, on skin injury due to vinorelbine extravasation in rats.

METHODSSkin injury due to vinorelbine extravasation was induced in the lower extremities of 30 SD rats, which were treated subsequently with topical DMSO, intralesional hyaluronidase, their combination, topical saline, and intralesional saline, with the rats without any treatment as the control. The wound area on 1, 4, 8, 12, 18, 24, 30 days and the time of healing were observed and compared.

RESULTSThe wound area on 1, 4, 8, 12, 18, and 24 days were significantly smaller in topical DMSO group than in topical saline and control groups (P<0.05), and so in intralesional hyaluronidase group than in intralesional saline and control groups (P<0.05), but there was no significant difference between single agent (hyaluronidase and DMSO) treatment group and the combined treatment group. The healing time was significantly shorter in topical DMSO and intralesional hyaluronidase groups than in topical and intralesional saline groups and control group ( 24.9-/+3.2 and 21.9-/+3.0 days vs 29.8-/+2.6, 28.6-/+4.1 and 30.6-/+3.0 days, P<0.01), but comparable between the two single agent groups and combined treatment group (23.3-/+3.8 days).

CONCLUSIONIntralesional hyaluronidase and topical DMSO application are effective therapies for skin damage due to vinorelbine extravasation, and their combination does not improve the therapeutic effect.

Administration, Topical ; Animals ; Dimethyl Sulfoxide ; administration & dosage ; pharmacology ; Drug Therapy, Combination ; Female ; Hyaluronoglucosaminidase ; administration & dosage ; pharmacology ; Injections, Intralesional ; Male ; Rats ; Skin ; drug effects ; injuries ; pathology ; Time Factors ; Vinblastine ; analogs & derivatives ; pharmacology ; Wound Healing ; drug effects

We think the strategy of classic natural product-based drug discovery will be an effective way for us to develop new drugs with independent intellectual property. The strategy includes: to study the molecular mechanism of action of classic natural product with chemical genetics and chemical biology approaches firstly; then establish the proper in vitro bioassay or bioassay system based on its molecular mechanism for their pharmacodynamic evaluation; finally, study their structure-activity, structure-toxicity and structure-ADME properties with medicinal chemistry.
Animals ; Anti-HIV Agents ; chemical synthesis ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; pharmacology ; Biological Products ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; pharmacology ; Drug Discovery ; Humans ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Oleanolic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology ; Triterpenes ; chemical synthesis ; pharmacology ; Vinblastine ; analogs & derivatives ; chemical synthesis ; pharmacology

BACKGROUND AND OBJECTIVEHuman telomerase reverse transcriptase is the catalytic subunit of telomerase, and its activity is correlated with cell's sensitivity to chemotherapy. The aim of this study is to investigate the differential expression of human telomerase reverse transcriptase (hTERT) mRNA in human lung adenocarcinoma cell line Anip973 and Anip973/NVB, and to observe the correlation between hTERT mRNA and drug-resistance.

METHODSThe real-time fluorescence quantitative RT-PCR was used to detect the change of hTERT mRNA in human lung adenocarcinoma drug-resistant cell Anip973/NVB and parental cell Anip973 treated by NVB.

RESULTSIn the control group, the expression of hTERT mRNA showed no significant difference between drug-resistant cell Anip973/NVB and parental cell Anip973. After been treated by NVB, the expression of hTERT mRNA in parental cell was significantly decreased (P < 0.01), and drug-resistant cell Anip973/ NVB had no evidently variant (P > 0.05). The down-regulated hTERT mRNA in Anip973 cell was higher than that in Anip973/ NVB cell.

CONCLUSIONTelomerase correlates with the drug-resistant cell A973/NVB, and telomerase may be a new target for multi-drug resistant inversion.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; genetics ; physiology ; Humans ; Lung Neoplasms ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Telomerase ; genetics ; Vinblastine ; analogs & derivatives ; pharmacology

MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF), suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study, quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells.
Animal ; Antineoplastic Agents/pharmacology ; Arsenites/pharmacology ; Carcinoma/drug therapy ; Drug Resistance, Multiple/physiology* ; Drug Resistance, Neoplasm/physiology ; Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/drug effects* ; Heat-Shock Proteins/antagonists & inhibitors ; Leukemia, Experimental/drug therapy ; Mice ; P-Glycoprotein/genetics ; P-Glycoprotein/drug effects ; Quercetin/pharmacology* ; Sodium Compounds/pharmacology ; Tumor Cells, Cultured ; Vinblastine/pharmacology ; Vincristine/pharmacology

Anthracyclines ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Humans ; Taxoids ; administration & dosage ; Vinblastine ; administration & dosage ; analogs & derivatives