OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

Bufanolides ; therapeutic use ; Hematologic Neoplasms ; drug therapy ; Humans ; Recurrence

Bufalin is an active compound of the traditional Chinese medicine Chansu, which exhibits significant anti-tumor activities in many solid tumors and leukemia cell lines. Bufalin could introduce apoptosis, reverse drug-resistance, and prevent migration and invasion of tumor cells. This paper reviewed the latest research progress of the in vitro and in vivo anti-tumor effect and mechanism of bufalin on a series of cancers, such as hepatocellular carcinoma, lung cancer, colon cancer, gastric cancer, leukemia, bladder cancer, and its formulation study is also summarized for the reference of its further study and application.
Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Bufanolides ; chemistry ; pharmacology ; therapeutic use ; Chemistry, Pharmaceutical ; methods ; Neoplasms ; drug therapy ; pathology

AIM: To study the bufadienolides in the Chinese traditional drug "Ch'an Su" and their cytotoxic activity. METHOD: Various chromatographic techniques were used to isolate the constituents, and their structures were elucidated through physical and spectroscopic data. RESULTS: Twenty compounds were isolated, and eighteen were evaluated in vitro for their cytotoxic activity against A-549 and K-562 cells. CONCLUSION Compound 1 (bufalin 3β-acrylic ester) was a new bufadienolide and exhibited the most potent activity against the two tumor cell lines with IC50 values of 7.16 and 6.83 nmol · L(-1). The relationships between structure and activity are discussed.
Amphibian Venoms ; chemistry ; pharmacology ; therapeutic use ; Antineoplastic Agents ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Bufanolides ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Humans ; Inhibitory Concentration 50 ; K562 Cells ; Medicine, Chinese Traditional ; Molecular Structure ; Neoplasms ; drug therapy ; Structure-Activity Relationship

OBJECTIVETo re-evaluate the effects of different "cocktail therapy" to prevent from phlebitis induced by Chansu injection.

METHODPatients treated with Chansu injection were divided randomLy into 4 groups with 90 per group, control group, phentolaminum group, the magnesium sulfate group-phentolaminum group, and anisodamine-phentolaminum group. Patients in the control group only received the routine nursing treatment, and patients in the various experiment group received different interventions. The comparison was made in the morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain.

RESULTThe morbidity of phlebitis was 8%, 8%, 6%, respectively. The starting time of phlebitis occurrence was (22 +/- 4), (27 +/- 5), (28 +/- 7) h, respectively. The NRS of pain was (4.75 +/- 1.51), (3.27 +/- 1.02), (2.71 +/- 1.63), respectively. The duration time of pain was (4.25 +/- 1.36), (2.51 +/- 1.05), (2.19 +/- 1.13) d respectively. In control group, the morbidity of phlebitis, the starting time of occurrence of phlebitis, the severity of pain, duration of pain was 30%, (16 +/- 4) h, (6.34 +/- 1.21), (5.47 +/- 1.07) d, respectively. As compared with the control group, a significance difference was found between every group in three test groups and control group respectively (P<0.05).

CONCLUSIONThe morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain was significantly reduced respectively by two different "cocktail therapy".

Adult ; Aged ; Animals ; Anura ; Bufanolides ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Humans ; Magnesium Sulfate ; therapeutic use ; Male ; Middle Aged ; Phentolamine ; therapeutic use ; Phlebitis ; drug therapy ; etiology ; prevention & control ; Solanaceous Alkaloids ; therapeutic use ; Young Adult

OBJECTIVETo re-evaluate the effects of different treatments to prevent from phlebitis induced by Chansu injection.

METHODPatients treated with Chansu injection were divided randomly into 4 groups with 50 per group, control group, the magnesium sulfate group, phentolaminum group, and anisodamine group. Patients in the control group only received the routine nursing treatment, and patients in the various experiment group received different interventions. The comparison was made in the morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain.

RESULTThe morbidity of phlebitis was 8%, 8%, 6% respectively. The starting time of phlebitis occurrence was (21 +/- 9.31) , (22.34 +/- 10.15), (20.19 +/- 11.23) h, respectively. The NRS of pain was (4. 15 +/- 1.03), (3.26 +/- 1.17), (4.32 +/- 1.36), respectively. The duration time of pain was (4.05 +/- 1.21), (3.37 +/- 1.17), (3.19 +/- 1.67) d, respectively. In control group, the morbidity of phlebitis, the starting time of occurrence of phlebitis, the severity of pain, duration of pain was 24%, (17 +/- 6.32) h, (6.58 +/- 1.29), (5.32 +/- 1.12) d, respectively. As compared with the control group, a significance difference was found between every group in three test groups and control group respectively (P<0.05).

CONCLUSIONThe morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain was significantly reduced respectively by external appication of magnesium sulfate, anisodamine, and intravenous drip infusion of phentolaminum.

Adult ; Aged ; Aged, 80 and over ; Bufanolides ; adverse effects ; Female ; Humans ; Infusions, Intravenous ; Magnesium Sulfate ; therapeutic use ; Male ; Middle Aged ; Morbidity ; Phentolamine ; administration & dosage ; Phlebitis ; chemically induced ; prevention & control ; Solanaceous Alkaloids ; therapeutic use ; Time Factors

OBJECTIVETo observe effects of cold- and hot-property herbs and effects of hot and cold constitutions on the tumor growth of tumor bearing rats, and to observe the effect of Cinobufacini Injection (CI) on the tumor growth of tumor bearing rats of different constitutions.

METHODSEighty healthy male Wistar rats were randomly divided into eight groups, i.e., the tumor bearing control group, the tumor bearing heat syndrome group, the tumor bearing cold syndrome group, the heat syndrome tumor bearing group, the cold syndrome tumor bearing group, the tumor bearing CI group, the heat syndrome tumor bearing CI group, and the cold syndrome tumor bearing CI group, respectively. The weight and volume of rats' subcutaneous tumor were measured 14 days after tumor inoculation.

RESULTSThe weight and volume of tumor in the heat syndrome tumor bearing CI group [(3.55 +/- 1.12) g, (2864.44 +/- 1430.51) mm3] and the tumor bearing CI group [(4.29 +/- 1.14) g, (3397.19 +/- 1701.13) mm3] were significantly lower than those of the tumor bearing control group [(6.01 +/- 2.45) g, (6218.91 +/- 3837.64) mm3] and the cold syndrome tumor bearing CI group [(6.90 +/- 1.57) g, (6168.42 +/- 2457.03) mm3], showing statistical difference (P<0.05). There was insignificant difference among other groups.

CONCLUSIONSCI showed better tumor inhibition effects on tumor bearing rats of heat syndrome constitution, which indicated CI was of cold property. It might be possibly used in tumor bearing rats of heat syndrome constitution.

Animals ; Bufanolides ; pharmacology ; therapeutic use ; Injections ; Male ; Neoplasms, Experimental ; drug therapy ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of traditional Chinese medicine (TCM) on quality of life (QOF) and survival period in patients with progressive gastric cancer, and thus exploring its clinical efficacy.

METHODSTCM therapy applied in the 34 patients assigned in the TCM group (Group I ) included intravenous injection of Cinobufotalin, beta-elemene, or orally taking of anti-cancer Chinese herbs. The same TCM was also applied in the 36 of the combined treatment group (Group II), but in combined use of FOLFOX chemotherapeutic protocol. Twenty-one days was taken as one cycle and all the patients received 2 cycles of treatment.

RESULTSThe median survival period in group II was 31 months, while it was 30 months in group I; the 1-, 2-, 3-year survival rates in group II were 88.89%, 84.38% and 59.26%, and those in the group I were 82.35%, 71.43% and 65.00%, respectively with insignificant difference between the two groups (chi2 = 0.298, P > 0.05); QOF in group I was significantly superior to that in group II (P < 0.05), and the adverse reaction occurrence was significantly less in Group I than that in group II.

CONCLUSIONChinese medicine treatment can improve the QOF and prolong the survival period of patients with progressive gastric cancer with few side effects.

Adenocarcinoma ; drug therapy ; mortality ; Adult ; Aged ; Bufanolides ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Phytotherapy ; Quality of Life ; Retrospective Studies ; Sesquiterpenes ; therapeutic use ; Stomach Neoplasms ; drug therapy ; mortality ; Survival Analysis ; Survival Rate

OBJECTIVETo study the antitumor effects of Chansu injection on transplanting- tumor of S(180 ) in mice and human colon cancer HT-29 in nude mice.

METHODSUsing transplanting- tumor models of S(180 ) in mice and human colon cancer HT-29 in nude mice,the tumor inhibitive ratio(IR) of Chansu injection was determined and apoptosis was microscopically observed.

RESULTSCompared with tumor-negative control groups, IR at different dosage of Chansu in models of S(180) and HT-29 was 19.1% - 38.2% and 9.5% - 15.8% respectively,there was a dose-dependent relationship in models of S ( 180) (P< 0.05) and HT- 29 (P> 0.05). The tumor growth was markedly inhibited by cyclophosphamide (CTX) in model of S( 180) with IR of 70.7% and in model of HT-29 with IR of 67.1%, compared with control groups, both P< 0.01; apoptosis induced by CTX was markedly observed by in microscope examination. No significant side effects were shown in the study group.

CONCLUSIONSChansu injection can significantly inhibit tumor growth in model of S(180), but not in model of HT- 29. Different type of tumor has different drug-sensitivity.

Animals ; Bufanolides ; pharmacology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; HT29 Cells ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred Strains ; Mice, Nude ; Sarcoma 180 ; drug therapy ; Xenograft Model Antitumor Assays