Alkaloids ; pharmacology ; Cisplatin ; pharmacology ; Fluorouracil ; pharmacology ; Hep G2 Cells ; Humans ; Quinolizines ; pharmacology ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; metabolism

N-Benzyl matrinol was obtained by hydrolysis, benzylation and reduction reaction from matrine. A series of hybrids (8a-8n) from (phenylsulfonyl)furoxan and N-benzyl matrinol were synthesized and biologically evaluated as anti-hepatocellular carcinoma agents. All target compounds were evaluated for anti-proliferative activity against human hepatocellular Bel-7402, SMMC-7721, Bel-7404, and HepG2 cells in vitro by MTT method. The results indicated that all of these compounds had potent anti-proliferative activity which were more potent than their parent compound and 5-FU, especially 8a-8h and 8j showed the strongest anti-HCC HepG2 cell activity with IC50 values of 0.12-0.93 μmol x L(-1).
Antineoplastic Agents ; pharmacology ; Carcinoma, Hepatocellular ; Fluorouracil ; Hep G2 Cells ; Humans ; Liver Neoplasms ; Oxadiazoles ; pharmacology

OBJECTIVETo evaluate the effect of melittin and 5-Fu, DDP, and TXT on human gastric cancer cell line BGC-823 and to primarily explore their possible mechanisms.

METHODSMedian effect analysis was employed to determine the interaction between melittin and 5-Fu, DDP, TXT by analyzing the relationship between fraction affected (FA) and the combination index (CI) acquired from the dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC-823 cells with or without treatment were measured by real-time fluorescent quantitative PCR.

RESULTS(1) Both melittin and chemotherapeutic agents inhibited the growth of BGC-823. (2) For BGC-823 cells were acted by 5-Fu +melittin, when FA ranged between 0.35-0.75, CI was less than 1. For BGC-823 cells were acted by DDP + melittin, when FA ranged 0.55 or so, CI = 1; when Fa ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT + melittin, CI less than 1 could be seen in the whole interval. (3) After treatment suppressed were the expressions of chemotherapeutic agent-associated genes of BGC-823 cells such as thymidylate synthetase (TS), excision repair cross-complementing gene 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), beta-tubulin III (TUBB3), and microtubule-associated protein tau (MAPT).

CONCLUSIONSMelittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents. The possible mechanisms might be associated with down-regulating chemotherapeutic agent-associated genes.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Synergism ; Fluorouracil ; pharmacology ; Humans ; Melitten ; pharmacology

OBJECTIVE: To observe the effect of garlic oil combined with 5-FU induced apoptosis of adenoid cystic carcinoma cell line ACC-M. METHOD: Human salivary in adenoid cystic carcinoma cell line AC-M was cultured, divided into the experimental group (5-FU group, garlic oil group, garlic oil + 5-FU group) and the control group, to observe the growth activity of tumor cells by MTT methods; to analyse the changes of cell cycle and apoptosis rate by flow cytometry. RESULT: MTT experiments showed that 5-FU, garlic oil, garlic oil and 5-FU on ACC-M cells have inhibition in different concentration, with the increase of concentration and action time of the rise; Cell cycle analysis showed significant changes in flow cytometry. With the increase of concentration and the acting time, the G0/G1, phase of the cell ratio increased, S had no significant change, but G2/M phase cells decreased. Apoptosis rate display showed garlic oil combined with 5-FU induced apoptosis of ACC-M cells was significantly stronger than single group. CONCLUSION Garlic oil can effectively induce the apoptosis of adenoid cystic carcinoma cell line ACC-M. The effect of garlic oil combined with 5-FU on ACC-M cells was stronger than the garlic oil, 5-FU used alone.
Allyl Compounds ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Adenoid Cystic ; pathology ; Cell Line, Tumor ; Fluorouracil ; pharmacology ; Humans ; Sulfides ; pharmacology

OBJECTIVETo propose a simple and practical method for preparing a mouse model of oligo-astheno-terato-spermia/azoospermia, and to offer a methodological suggestion for the studies on the related mechanism of spermatogenesis and evaluation of medication efficacy by observing the early changes of testis morphology after 5-fluorouracil treatment.

METHODSMice were injected with a single dose of 5-flourouracil at 250 mg/kg via the tail vein, and their testes were harvested and paraffin sections prepared before and 3, 7, 11 and 14 d after the injection to be observed for the morphological changes by hematoxylin and eosin staining.

RESULTSThe numbers of spermatocytes/spermatids were progressively reduced inside the testis seminiferous tubules of the mice at 3, 7 and 11 d after the 5-fluorouracil injection, and the tubule walls became thinner, which reached the nadir at 11 d, with evident swelling and crazing of the seminiferous tubules. At 14 d, the swelling almost disappeared and spermatocytes became repopulated, while the flaws still existed in the seminiferous tubules and no mature sperm were seen.

CONCLUSIONOne-dose injection of 5-fluorouracil via the tail vein might be a simple and effective method for preparing the animal model of reproductive function damage induced by chemotherapeutic medication.

Animals ; Fluorouracil ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Testis ; anatomy & histology ; drug effects

OBJECTIVETo explore the potential markers of colorectal cancer metastasis and the influence of 5-FU on differentially expressed proteins by using proteomic technology, and to elucidate the mechanism of colorectal cancer metastasis.

METHODSHuman colorectal carcinoma cell lines of different metastatic potential, Lovo and SW480 were conventionally cultured, and the protein was extracted. 50% inhibitory concentration (IC(50)) of 5-FU to these two cell lines was measured by MTT assay. Proteins of these two cell lines after intervention by 5-FU at IC(50) were extracted, then 2-dimensional gel electrophoresis was conducted for the proteins. The differential protein spots were examined by mass spectrometry and analyzed by bioinformatics. Difference of expressed proteins in two cell lines before and after the intervention of 5-FU was validated by Western blot and immunofluorescence.

RESULTSEleven differentially expressed proteins were identified by 2-dimensional gel electrophoresis and mass spectrometry. The hnRNP K protein and PDI were selected to be examined by Western blot and immunofluorescence. Results revealed that the expression of hnRNP K in Lovo was higher than that in SW480, while the expression of PDI was lower in Lovo. After intervention by 5-FU at IC(50), the expression of hnRNP K in Lovo decreased more as compared to SW480, while the expression of PDI in SW480 increased more as compared to Lovo.

CONCLUSIONThere are significant differences in expression of hnRNP K and PDI proteins between Lovo and SW480 cell lines, and the proteins alter regularly after 5-FU intervention.

Biomarkers, Tumor ; blood ; Cell Line, Tumor ; Colorectal Neoplasms ; metabolism ; pathology ; Fluorouracil ; pharmacology ; Humans ; Neoplasm Metastasis ; Proteomics

OBJECTIVETo investigate the reversing effects of curcumin on hepatocellular carcinoma drug resistance Bel7402/5-Fu cell line.

METHODSThrough the exposure to gradual increased concentrations of 5-fluorouracil (5-Fu), the cell line Bel7402 was induced to establish a multi-drug resistant sub-cell line Bel7402/5-Fu. The sensitivity to 6 chemotherapeutics of Bel7402 and Bel7402/5-Fu were detected using methyl thiazolyl tetrazolium (MTT) assay. The 50% inhibitory concentration (IC50) and resistant index (RI) were calculated. The differences of the inhibition ratio of Bel7402/5-Fu by curcumin, 5-Fu, curcumin combined with 5-Fu were detected using MTT assay. The effects of curcumin, 5-Fu, curcumin combined with 5-Fu on the Bel7402/5-Fu apoptosis were detected using flow cytometry.

RESULTSThe Bel7402/5-Fu cell line showed multi-drug resistance (MDR) to various chemotherapeutics, with the highest RI shown of 5-Fu (being 109.55 +/- 14.30 times). The inhibition ratio of 5, 10, and 20 microg/mL curcumin combined with 5-Fu (50% IC50) was respectively 21.47% +/- 1.49%, 27.10% +/- 2.32%, and 59.37% +/- 2.45%. The Bel7402/5-Fu apoptosis ratio of 5, 10, and 20 microg/mL curcumin combined with 5-Fu (50% IC50) was 30.92% +/- 2.10%, 44.87% +/- 2.24%, and 50.36% +/- 2.58%, respectively, which was obviously higher than that of the curcumin group and the 5-Fu group. Besides, the apoptosis rate increased along with increased curcumin concentration in the range of 0 -20 microg/mL.

CONCLUSIONCurcumin could induce the apoptosis of Bel7402/5-Fu. Meanwhile, it showed favorable reversing effects on MDR.

Cell Line, Tumor ; Curcumin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Fluorouracil ; pharmacology ; Humans

This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.
Mice ; Animals ; Tumor Microenvironment ; Colonic Neoplasms/genetics* ; Fluorouracil/pharmacology* ; Polysaccharides/pharmacology* ; CD8-Positive T-Lymphocytes/metabolism* ; RNA, Messenger/metabolism*

A new chromene (1) and six known compounds identified as 6-hydroxymellein (2), 6-hydroxy-5-methylmellein (3) nectriapyrone (4), chermesinone A(5), chermesinone B(6), and pomopxanthone A(7), were isolated in our investigation of the cytotoxic constituents from the fermented rice substrate of endophytic fungus Phomopsis sp. HCCB03519. The structures of these com pounds were elucidated through spectroscopic data analysis. All compounds exhibited inhibitory activities against cancer cell lines. Compound 7 showed stronger inhibition against cancer cells than the positive control 5-Fu.
Antineoplastic Agents ; chemistry ; pharmacology ; Ascomycota ; chemistry ; Benzopyrans ; chemistry ; pharmacology ; Cell Line, Tumor ; Fluorouracil ; chemistry ; pharmacology ; Humans ; Isocoumarins ; chemistry ; pharmacology ; Molecular Structure

OBJECTIVETo study the effect of angiogenesis inhibitor and its combine with chemical drug in suppressing the growth of adenoid cystic carcinoma (ACC).

METHODSAcc-M cells were inoculated subcutaneous into BABL/C nu/nu mice. The mice were divided into control, different dose of TNP-470 treatment groups, 5-Fu treatment group and TNP-470 plus 5-Fu treatment group. Treatments were given 48 hours after inoculation. The mice were sacrificed on the 22nd day and excised tumors were weighted. Tumors were also investigated by immunohistochemistry and ultrastructural observations.

RESULTSTNP-470 100 mg/kg/qod efficiently inhibited the growth of Acc-M tumors. TNP-470 30 mg/kg/qod combined with 50 mg/kg/week 5-Fu also resulted in significant growth inhibit of the tumors. TNP-470 suppressed tumor growth by inhibiting neovascularization, therefore inducing apoptosis of Acc-M cells. All experimental groups had different degrees of VEGF and bFGF express.

CONCLUSIONSince ACC is a slow developing tumor, blood supply is not so sufficient as sarcomas. Angiogensis inhibitor may inhibit its growth in high dosage. Combining medium dosage of angiogensis inhibitor with chemical drug may have synergistic result in inhibiting ACC growth.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; Carcinoma, Adenoid Cystic ; drug therapy ; Cell Line, Tumor ; Cyclohexanes ; pharmacology ; Fluorouracil ; pharmacology ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; pharmacology