Analysis of the nature, tastes, channel distributions and effects of the frequently used herbal medicines in the prescriptions involved in the clinical literatures about treatment of gastric cancer published from 1988 to 2007 was made in the paper. The literatures were categorized into three types: 1) treatment of middle- and late-stage gastric cancer; 2) prevention and treatment of the recurrence and metastasis after operation; 3) Chinese herbal medicines combined with chemotherapy for enhancing efficacy and reducing toxicity. The most frequently used herbal medicines in the three literature types were qi-invigorating herbs, such as Atractylodes, Astragalus, Codonopsis, Glycyrrhiza and Ginseng, etc. The herbal medicines for promoting urination to subside swelling such as tuckahoe and Semen Coicis, etc were used more frequently than the herbal medicines for regulating qi such as dried orange peel and putchuck, etc, as well as for clearing away heat to remove toxin such as spreading hedyotis herb, Herba Scutellariae Barbatae, yangtao actinidia root, and Rhizoma Paridis, etc. From another angle, the most frequently used herbal medicines for the treatment of gatric cancer were those cold, warm and neutral in nature, sweet, bitter and pungent in taste, and distributed to spleen and liver channels.

Advanced gastric cancer has a low survival rate while traditional Chinese medicine (TCM) therapy has effects in inhibiting tumor growth, lengthening survival time and improving the quality of life.

OBJECTIVE: To investigate the mechanism of Chinese herbal recipe Weichang'an (WCA) in inducing cell apoptosis of human gastric cancer grafted onto nude mice. METHODS: The high performance liquid chromatography was used for monitoring the stability of WCA. A human gastric cancer cell line SGC-7901 grafted in nude mouse was used as the animal model. The mice were divided into untreated group and two experimental groups. Animals in the two experimental groups received either WCA over a 34-day period or 5-fluorouracil (5-FU) over a 6-day period starting at the 8th day after grafting. Animals in the untreated group received normal saline on an identical schedule. Animals were killed 41 days after being grafted. To assess the effect of the treatment on tumor, the tumor weight was determined by the electron balance immediately after the animals were killed. SP immunohistochemical method was used to detect the expression of proliferating cell nuclear antigen (PCNA) in grafts. Apoptotic indices (AI) of the tumor cells were examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. SP method was also used to detect the expressions of cleaved caspase-3, caspase-8 and caspase-9. SYBR green dye I real-time quantitative polymerase chain reaction (real-time quantitative [corrected] PCR) was used to assess the related gene alterations in mRNA level. The expressions of phospho-Stat3 (Tyr705) and bcl-2 proteins were detected by using SP method. RESULTS: Compared with the untreated group, tumor growth was significantly inhibited by treatment of WCA or 5-FU (P<0.01, respectively). The tumor inhibition rate in the WCA-treated group was 48.70% and that in the 5-FU-treated group was 60.10%. The average labeling index (LI) for PCNA in the WCA-treated group and 5-FU-treated group was significantly decreased as compared with that in the untreated group, respectively. The AI of human gastric cancer grafted in the nude mice detected by using TUNEL method was significantly increased to (9.72+/-4.51)% in the WCA-treated group, while it was (2.45+/-1.37)% in the untreated group. 5-FU-treated group was also found a significantly increased AI compared with the untreated group. The expressions of cleaved caspase-3 and caspase-9 in the WCA-treated group and 5-FU-treated group were significantly increased as compared with those in the untreated group. But caspase-8 showed no significant alteration either in the WCA-treated group or in the 5-FU-treated group. The expression levels of Stat3 (2(-)delta delta C(T))=0.16) and bcl-2 (2(-)delta delta C(T))=0.10) detected by using real-time quantitative [corrected] PCR were lower in the WCA-treated group than those in the untreated group. The expressions of phospho-Stat3 (Tyr705) and bcl-2 in the WCA-treated group were significantly decreased as compared with those in the untreated group. CONCLUSIONS: Chinese herbal recipe WCA can inhibit gastric cancer cell SGC-7901 growth in vivo, induce gastric cancer cell apoptosis and suppress the cell proliferation. WCA induces apoptosis through the caspase-9 and caspase-3 pathway in vivo. Its mechanism might be involved in the down-regulation of Stat3 and bcl-2 genes.

OBJECTIVE: To evaluate the growth-inhibiting and anti-metastasis effects of Weichang'an Decoction (WCAD) on orthotopic transplant nude mouse model of human gastric cancer. METHODS: Forty-one nude mice were implanted with SGC-7901 cells at orthotopic site, whereas 25 were implanted with SGC-7901 cells subcutaneously. Then the nude mice in each transplantation model were divided into the same three groups which were WCAD-treated group with WCAD 0.5 ml/d taken orally, 5-FU-treated group with 5-FU 50 mg/kg intraperitoneally injected weekly and untreated control group with physiological saline 0.5 ml/d taken orally. The growth-inhibiting rates of transplant tumors were detected and the metastatic lesions were examined in the orthotopic transplant mouse model while PCNA-positive rate and apoptotic index (AI) were observed in the subcutaneous transplant mouse model. RESULTS: The growth-inhibiting rates in the WCAD-treated and 5-FU-treated groups of orthotopic transplant mouse model were 40.82% and 37.92% respectively whereas those of subcutaneous transplant mouse model were 48.70% and 60.10%. The incidence rates of metastasis in perigastric lymph notes, lymph nodes in the porta hepatis, liver, diaphragm and peritoneum in the WCAD-treated and 5-FU-treated groups were lower than those in the untreated control group, and the total metastasis rates in the WCAD-treated, 5-FU-treated and the untreated control groups were 30.77%, 28.57% and 71.43% respectively with significant differences (P<0.05). The total PCNA-positive rates in the WCAD-treated and 5-FU-treated groups were obviously lower than that in the untreated control group (P<0.05 or P<0.01) while the AI was higher than that in the untreated control group (P<0.01). The growth-inhibiting rate, total PCNA-positive rate and total metastasis rate in the WCAD-treated group had no significant differences as compared with those in the 5-FU-treated group, but the AI in the WCAD-treated group was significantly higher than that in the 5-FU-treated group (P<0.05). CONCLUSION: WCAD has the inhibiting effects on tumor growth and metastasis of gastric cancer which is orthotopic implanted onto nude mice. This effect may be obtained by proliferation suppression and apoptosis induction in cancer.

The incidence of colorectal cancer is high among the elderly. Traditional Chinese medicine (TCM) has been widely used in the treatment for colorectal cancer of old people. However, controlled trials with large sample size evaluating the effect of TCM are rare.

Gastric cancer is one of the most common malignant tumors. Traditional Chinese medicine (TCM) has been widely used in treatment of gastric cancer, but still lacking large sample controlled trial to evaluate its efficacy.

OBJECTIVEChinese jianpi herbal recipe Weichangan (WCA) could increase the survival rate of advanced gastric cancer. This study was designed to investigate the molecular mechanism of WCA in treatment of gastric cancer by cDNA array, real-time quantitative PCR and immunohistochemical technique.

METHODA human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mouse was used as the animal model. The mice were divided into 3 groups, one control and the two representing experimental conditions. Animals in the two experimental groups received either WCA over a 34-day period or 5-fluorouracil (5-FU) over 6-day period starting at 8th day after grafting. Control animals received saline on an identical schedule. Animals were killed 41 days after being grafted. To assess the effect of therapy tumor weight was determined by a electron balance immediately after the animals killed. SP immunohistochemical method was used to detect the expression of proliferating cell nuclear antigen (PCNA) in xenografts. For detection of apoptotic cells, apoptotic indices (AI) were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. SP method was also used to detect the expression of cleaved Caspase-3. The expression profiles in paired WCA treated gastric cancer samples and the N. S. control samples were studied by using a cDNA array representing 14, 181 cDNA clusters. The alterations in gene expression levels were confirmed by real-time quantitative PCR. SP method was used to detect the expression of Phospho-Stat3 (Tyr705) and bcl-2.

RESULTWhen compared with controls, tumor growth was significantly inhibited by treatment with the WCA or 5-FU (P < 0.01, respectively). The average of tumor inhibitory rate in WCA group was (44.32 +/- 5.67)% and 5-FU (47.04 +/- 11.33)%. The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group respectively. AI of human gastric cancer xenografts in nude mice was significantly increased to (9.72 +/- 4.51)% using TUNEL method in WCA group compared with the controls (2.45 +/- 1.37)%. 5-FU group was also found a significantly increased AI compared with the controls. The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively. There were 45 different expression ESTs among the control sample pool and WCA sample pool. There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated. These 45 ESTs contains 35 cloned genes and 11 unknown ESTs. By using Real-time Quantitative PCR, the expression level of Stat3 (2(-deltadeltaCT) = 0.16) , RIPX (2(-deltadeltaCT) = 0.18), ROD1 (2(-deltadeltaCT) = 0.23) and bcl-2 (2 (-deltadeltaCT) = 0.10) was lower in WCA group than that in control group respectively. The expression of Phospho-Stat3 (Tyr705) and bcl-2 in WCA group and 5-FU group was significantly decreased compared with the control group respectively.

CONCLUSIONChinese jianpi herbal recipe WCA could inhibit gastric cancer cell SGC-7901 growth in vivo. WCA could induce gastric cancer cell apoptosis and suppress proliferation. Its mechanisms might be involved in the down-regulation of Stat3, RIPX, ROD1 and bcl-2 gene.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Animals ; Antimetabolites, Antineoplastic ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Expressed Sequence Tags ; Fluorouracil ; pharmacology ; therapeutic use ; Gene Expression Profiling ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nerve Tissue Proteins ; metabolism ; Plants, Medicinal ; chemistry ; Polypyrimidine Tract-Binding Protein ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA-Binding Proteins ; metabolism ; STAT3 Transcription Factor ; metabolism ; Stomach Neoplasms ; drug therapy ; genetics ; pathology ; Xenograft Model Antitumor Assays ; methods