Zebularine induces apoptosis of esophageal cancer cells via demethylation SFRP2/Dkk3 to regulate Wnt/β-catenin signaling pathway / 药学学报

To explore the effect and mechanisms of demethylation drug zebularine on esophageal cancer cells apoptosis, ECA109 cells and KYSE170 cells were treated with zebularine at different concentrations (25, 50, 100, 200, and 400 μmol·L-1). The cell viability was measured by CCK-8. Flow cytometry was used to detect the cell apoptosis rate, Western blot was performed to determine the expression of apoptosis protein (Bcl-2, Bax, cleaved-caspase-3, and cleaved-PARP) and Wnt signal pathway molecules (β-catenin, cyclin D1, and c-Myc), real-time quantitative PCR was used to detect the expression level of negative regulatory genes of Wnt signaling pathway, methylation specific PCR (MSP) was used to detect the methylation status of secreted frizzled related protein 2 (SFRP2) and dickkopf 3 (Dkk3) genes. After knockdown of SFRP2 and Dkk3, the effect of zebularine on apoptosis was detected. The studies showed that zebularine could inhibit the activity of ECA109 and KYSE170 cells in a dose-dependent and time-dependent manner; zebularine could induce cell apoptosis, down-regulate the expression of Bcl-2 protein, up-regulate the expression of Bax, cleaved-caspase-3, and cleaved-PARP protein, and inhibit the expression of β-catenin, cyclin D1, and c-Myc protein (P < 0.05); the mRNA expression levels of Dkk3 and SFRP2 were significantly up-regulated by zebularine, while the methylation levels of SFRP2 and Dkk3 promoters were decreased; knockdown of SFRP2 and Dkk3 could reduce the apoptosis induced by zebularine. In summary, zebularine could reduce the methylation level of SFRP2 and Dkk3 gene promoter, promote the expression of SFRP2 and Dkk3 gene, and then induce the apoptosis of esophageal cancer cells by inhibiting Wnt/β-catenin signaling pathway.

Relationship between the expression of MMP-9, MMP-13, HIF-1α and clinical pathologic features, EGFR mutation and prognosis in lung adenocarcinoma / 临床与实验病理学杂志

Purpose To analyze the MMP-9,MMP-13,HIF-1α expression in lung adenocarcinoma tissue and to explore the relationship with clinical pathologic features,EGFR mutation and prognosis of the patients.Methods The expression of MMP-9,MMP-13,HIF-1α in 629 cases of lung adenocarcinoma were detected by using immunohistochemical of SP method.50 cases of normal tissue adjacent to carcinoma and 50 cases of pneumonia pseudotumor hyperplasia tissues were selected as controls.629 patients with lung adenocarcinoma were detected by real-time fluorescence quantitative PCR and all of them were followed-up.Results The MMP-9,MMP-13,HIF-1α expression in lung adenocarcinoma tissues were higher than controls (P ＜ 0.001).The MMP-9 expression was correlated with lymph node metastasis and the size of the tumor (P ＜ 0.05).The MMP-13 expression was correlated with smoking history,TNM stage,lymph node metastasis and the size of the tumor (P ＜0.05).The HIF-1α expression were correlated with smoking and lymph node metastasis.Statistically significant differences were found in all these above groups (P ＜ 0.05).But the expression of all has nothing to do with the EGFR mutation (P ＞0.05).The Kaplan-Meier survival analysis results showed that MMP-9,MMP-13,HIF-1α positive expression groups of 12,24 and 36 months cumulative survival were significantly lower than the negative expression groups.COX multiple factor analysis results showed that EGFR mutation,the expression of MMP-9,MMP-13,HIF-1α,tumor size,TNM stage were independent risk factors for the development of lung adenocarcinoma patients living conditions.Statistically significant differences were found in these groups (P ＜0.05).Conclusion MMP-9,MMP-13,HIF-1α are overexpressed in lung adenocarcinoma tissues,and its expression are associated with lymph node metastasis,but has nothing to do with EGFR mutations.Patients with positive expression of MMP-9,MMP-13,HIF-1α and with no EGFR mutation have lower survival rates,and they are independent risk factors for the development of lung adenocarcinoma patients living conditions.

Effect of Tanreqing injection on immune activity of peripheral blood lymphocytes of patients with lung cancer / 中国中药杂志

To investigate the effect of Tanreqing injection on immune activity of peripheral blood lymphocytes of patients with lung cancer. The peripheral blood lymphocytes of patients with lung cancer and healthy persons were separated by the density gradient centrifugation method for subsequent experiments, with those from healthy persons as the positive control. The effect of Tanreqing injection on stimulating the proliferation of lymphocytes with phytohemagglutinin (PHA) was determined by MTT method. The effect of Tanreqing injection on the lymphocyte secretions of IFN-γ and TNF-α and the subset ratio of lymphocytes cultured separately or with Tanreqing injection of different concentrations were examined by ELISA and flow cytometry (FCM) respectively. In addition, the LDH release assay was used to detect the cytotoxicity of cytotoxic T cells (CTL) and natural killer cells (NK). According to the findings, all of immunological indexes of lymphocytes from patients with lung cancer were weaker than that of healthy persons, but with the obvious increases in proliferation activity and IFN-γ and TNF-α secretions of lymphocytes co-cultured with Tanreqing Injection (P < 0.05). Among lymphocyte subsets co-cultured with Tanreqing Injection, CD3+, CD3+ CD4+ and CD3- CD16 + 56+ cell ratios notably increased, whereas CD4+ CD25+ Treg cell ratio obviously decreased (P < 0.05). In the meantime, Tanreqing injection can markedly promote the cytotoxicities of CTL and NK (P < 0.05). In conclusion, Tanreqing injection shows a significant effect in promoting the immune activity of lymphocytes from patients with lung cancer and their anti-tumor immunity.

Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.</p><p><b>METHODS</b>The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.</p><p><b>RESULTS</b>A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P < 0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P < 0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P < 0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P < 0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age ≥ 50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.</p><p><b>CONCLUSIONS</b>The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the primary site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.</p>

Effect of topotecan on retinocytoma cell apoptosis and expression of Livin and PTEN / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Retinocytoma (RB) is a very common intraocular malignant tumor during infancy. Chemotherapy has gradually been used as the first-line treatment for intraocular RB in recent years. In this study, Livin and PTEN expressions were observed in the RB tissue, along with the growth-inhibiting and apoptosis-induced effects of topotecan (TPT) on RB HXO-Rb44 cell strain. This study aimed to investigate the antigrowth effects of TPT on RB cell strain HXO-Rb44.</p><p><b>METHODS</b>Max-Vision(TM) rapid immunohistochemistry was adopted to detect Livin and PTEN expressions in the normal retina and in RB, and their relationship with RB clinicopathologic features was analyzed. Human RB cell strain HXO-Rb44 was cultivated and passaged. MTT method was used to measure the survival rates of HXO-Rb44 cell strains under various TPT concentrations. IC50 values were calculated. Flow cytometry was used to detect the effects of various TPT concentrations on HXO-Rb44 cell apoptosis. Western blotting was used to detect the differences of Livin and PTEN protein expressions during cell apoptosis.</p><p><b>RESULTS</b>The positive expressions of Livin and PTEN in the RB group were obviously different from those in the normal control group. In RB tissue, Livin expression was relevant to PTEN expression. TPT could significantly induce the occurrence of cell apoptosis and had a dependent relationship with drug concentration. Livin and PTEN expression levels varied with the extension of the effect time of TPT based on Western blotting analysis.</p><p><b>CONCLUSIONS</b>Livin and PTEN have high and low expression levels in the RB tissue, respectively. Both of them have key roles in RB occurrence and development. TPT could induce human RB cell strain HXO-Rb44 cell apoptosis, and its mechanism is associated with the inhibition of Livin and PTEN expressions.</p>

Effect of microRNA-mediated p65 gene silencing on the proliferation and apoptosis of human breast cancer MDA-MB-231 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of microRNA (miRNA)-mediated p65 gene knockdown on the proliferation and apoptosis of human breast cancer MDA-MB-231 cells.</p><p><b>METHODS</b>p65-targeted miRNA plasmid was constructed and transfected into MDA-MB-231 cells via lipofectamine(TM)2000. The expression of p65 gene in the transfected cells at the mRNA and protein levels were detected by RT-PCR and Western blotting, respectively. The cell proliferation and apoptosis were measured by MTT assay and flow cytometry (FCM), respectively. The expressions of apoptosis-related proteins were detected by Western blotting in the transfected cells.</p><p><b>RESULTS</b>Compared with the negative control group, the expressions of p65 mRNA and protein in p65miRNA-trasnfected cells were significantly down-regulated (P<0.05). MTT assay showed significantly lowered viability of MDA-MB-231 cells after the transfection (P<0.05). FCM showed an increased cell apoptosis rate in p65miRNA group compared with that in the negative control group (P<0.05). Caspase-3 and PARP were both cleaved into their active forms and the expression of these active forms was increased in p65miRNA group.</p><p><b>CONCLUSION</b>The miRNA targeting p65 gene can inhibit the proliferation and induce apoptosis of breast cancer cells, and p65 gene might become a new target in gene therapy for human breast cancer.</p>

Expression of Foxp3~+ lymphocytes in breast carcinoma tissues and their clinic significance / 军事医学科学院院刊

Objective To investigate the expression of Foxp3~+ lymphocytes in breast carcinoma tissues and their correlation with other pathological factors,and to investigate the mechanism of action of Treg cells.Methods The expression of Foxp3~+ lymphocytes in the breast cancer tissue and non-cancerous tissue was detected by flow cytometry (FCM) in 30 breast carcinoma patients, and its correlation with other pathological factors was statistically analyzed by multiple linear regression analysis.The expression of TGF-β and IL-10 in the lymphocytes infiltrated in breast cancer tissue and non-cancerous tissue was measured by immunohistochemistry, and their correlation with the expression of Foxp3~+ lymphocytes was statistically analyzed by linear correlation dependability analysis. Results There was significant difference in the expression of Foxp3~+ lymphocytes between the malignant and non-cancerous breast tissues(P<0.05),and it was positively correlated with the clinical stage,blood vessel invasion and the matter of axillary lymph node metastasis(P<0.05). The expression of IL-10 in the tumor infiltrating lymphocytes was positively correlated with the expression of Foxp3~+ lymphocytes(P<0.05).Conclusion The expression level of Foxp3~+ lymphocytes is correlated with invasion and metastasis of breast carcinoma, and the IL-10 secreted by Foxp3~+ lymphocytes may be involved in this effect.Foxp3~+ lymphocytes can be used as an assistant marker for prediction and new therpeutic target of breast cancer.

Inhibitory effects of enhanced expression of CD40L in ovarian cancer OVHM cells on the liver metastases in mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To examine the in vivo anti-metastatic effect of enhanced expression of CD40L cDNA in murine ovarian cancer OVHM cells (CD40L-OVHM) injected into the spleen on liver metastasis in mice.</p><p><b>METHODS</b>OVHM cells were inoculated into the spleen of 6 to 8 week-old female B6C3F1 (C57BL/6N x C3H/He) mice. The established liver metastasis was identified by histopathology (HE staining). OVHM cells, DNA-pMKITneo-OVHM cells or CD40L-OVHM cells were inoculated into the spleen of female B6C3F1 mice and the expressions of CD11c in splenic cells were detected by flow cytometry. The specific cytotoxicity of splenic cells was detected by MTT assay, and the serum cytokines of IFN-gamma, TNF-alpha, IL-12, IL-4 and IL-10 of the mice were measured by enzyme linked immunoabsorbent assay. The liver metastases and the survival time of the mice were also recorded.</p><p><b>RESULTS</b>The mouse models with liver metastasis by injecting tumor cells into the spleen of mice were established. The expression of CD11c and the specific killing rate in CD40L-OVHM cells group was significantly higher than that in the OVHM cells group and DNA-pMKITneo-OVHM cells group. The expressions of IFN-gamma, TNF-alpha and IL-12 in the CD40L-OVHM cells group were much more increased than OVHM cells group and DNA-pMKITneo-OVHM cells group, but the expressions of IL-4 and IL-10 in the CD40L-OVHM cells group were decreased significantly (p < 0.05). The average weights of livers and spleens of mice in CD40L-OVHM cells group were significantly lower than those of DNA-pMKITneo-OVHM cells group and OVHM cells group. The survival time of mice in CD40L-OVHM cells group was also significantly longer than that in the OVHM cells group and DNA-pMKITneo-OVHM cells group (P < 0.05).</p><p><b>CONCLUSION</b>The data directly demonstrate that the expression of CD40L in ovarian cancer cells (CD40L-OVHM) can enhance the proliferation and differentiation of dendritic cells in the spleen and induce specific cytotoxic effect of T cells in the spleen, and may regulate the immune function of peripheral blood cells and the immune balance between Th1 cells and Th2 cells, which maybe the possible mechanism induced by CD40L in mice inhibiting the development of liver metastasis.</p>

Enhanced expression of CD40L cDNA on ovarian cancer cell line OVHM induces the secretion of Th1 cytokines from dendritic cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To examine whether the enhanced expression of CD40L cDNA on murine ovarian cancer (OVHM) cells could induce the secretion of Th1 cytokines from dendritic cells (DC).</p><p><b>METHODS</b>OVHM cells were transfected with the full-length mouse CD40L cDNA by lipofectamine 2000 and then G418 resistant cells as positive cells were selected. They were examined for their expression of CD40L with flow cytometry. Bone marrow cells were firstly depleted of erythrocytes, macrophages, T and B cells with PE-conjugated magnetic beads, and then cultured in 10% FCS RPMI 1640 medium supplemented with recombinant mouse GM-CSF and IL-4 for 10 days. PKH67-labeled tumor cells were cultured with DC, and then the stained cells were analyzed for the expression of MHC-I, MHC-II, CD80, CD86, CCR7 in DC with flow cytometry. The expression of p40, p19, p35, p28, EBI3 subunits, IL-18, IFN-gamma, Mig gene in cocultured DC-tumor cells were detected by RT-PCR.</p><p><b>RESULTS</b>The CD40L cDNA was successfully transfected into OVHM cells. Bone marrow-derived DCs, when cultured with CD40L/OVHM, formed clusters with the tumors and showed an upregulated expression of MHC- I, MHC-II, CD80, CD86, CCR7. Expression of the IL-12, IL-23, IL-27, IL-18, interferon-gamma (IFN-gamma) and Mig (monokine induced by IFN-gamma) genes was induced in the DCs that were cultured with CD40L/OVHM but not with OVHM cells.</p><p><b>CONCLUSION</b>These data directly showed that the expression of CD40L on ovarian cancer cells facilitates the interaction between DCs and tumors, enhances the maturation of DCs, induces secretion of Th1 cytokines, especially for IL-12, IL-23 and IL-27, which maybe one of the possible antitumor mechanism for CD40L-transfected ovarian cancer cell line.</p>

Effect of the venom of the spider Macrothele raveni on the expression of p21 gene in HepG2 cells / 生理学报

This paper focuses on the effect of the venom of the spider Macrothele raveni on the proliferation of human hepatocelluar carcinoma cell line HepG2 and the related molecular mechanism. XTT test showed that the proliferation of HepG2 cells in vitro was inhibited by the spider venom (P<0.05) in a concentration-dependent manner. By using flow cytometry, it was found that the spider venom caused selective G(2)/M cell cycle arrest in HepG2 cells. RT-PCR and Western blot indicated the expressions of p21 mRNA and protein in HepG2 cells were obviously up-regulated by the spider venom. The venom of the spider Macrothele raveni inhibited the proliferation of HepG2 cells. These results suggest that the possible mechanism of the spider venom is to activate the expressions of p21 gene and protein and to cause selective cell cycle arrest at G(2)/M phase, leading to HepG2 cell apoptosis.

Effect of IL-24 gene expression on the growth of glioma cells in vitro and in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of IL-24 expression on the growth of glioma cells.</p><p><b>METHODS</b>The IL-24 gene was transfected into rat glioma C6 cells with a retroviral vector. The expression of IL-24 in C6/IL-24 glioma cells was confirmed by RT-PCR. MTT assay and flow cytometry were used to study tumor cell proliferation in vitro. Tumorigenicity in vivo was studied in inbred SD male rats by the growth of intracerebrally inoculated tumor.</p><p><b>RESULTS</b>It was confirmed by RT-PCR that the exogenous IL-24 gene expressed in C6/IL-24 cell. The C6/IL-24 cell proliferation in vitro and tumorigenicity in vivo were both inhibited compared with its parental C6 cell.</p><p><b>CONCLUSION</b>IL-24 expression in glioma cells somehow inhibits their growth in vitro and in vivo.</p>

Clinical observation on treatment of cancerous hydrothorax by aiyishu injection / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of Aiyishu Injection (AYSI) on cancerous hydrothorax, quality of life (QOF), and cellular immune function of patients.</p><p><b>METHODS</b>Sixty late-stage cancer patients accompanied hydrothorax were randomly divided into the experimental group (EG) and the control group (CG), with thirty patients in each group. After thoracenteses being carried out in all patients for draining off hydropsy, to the patients in EG, AYSI was medicated, 50 ml by intrathoracic and another 50 ml by intravenous injection; while to the patients in CG chemotherapeutic agent or interleukin-2 (IL-2) was given. The same treatment, thoracentesis and medication, was repeated 3 days later. After 4 weeks, the volume of pleural effusion was measured with B-mode ultrasound to evaluate the therapeutic effects of AYSI. QOF, body weight and T-lymphocyte subsets were compared between the two groups before and after treatment.</p><p><b>RESULTS</b>The clinical efficacy was significantly higher in EG than that in CG (P < 0.01). Besides, QOF was significantly improved (P < 0.05) and levels of CD3+ , CD4+ , CD4+ /CD8+ in peripheral blood increased in EG after treatment, which were significantly different to those in CG (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>AYSI has definite therapeutic effects on cancerous hydrothorax, it could improve QOF and cellular immune function in patients with cancer.</p>

Study on mechanism of the anti-tumor activity of Acanthopanax gracilistylus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the mechanism of anti-tumor activity of Acanthopanax gracilistylus extract (Age).</p><p><b>METHODS</b>The tumor cells proliferation was detected by using (3H)-TdR incorporation method, and the effects of Age on cell cycle of tumor cells, retinoblastoma (Rb) protein and cyclin-dependent kinases (Cdk) were analyzed by flow cytometry and Western blotting assay, respectively.</p><p><b>RESULTS</b>It was indicated by cytoactivity test in vitro that Age only had effect in inhibiting the proliferation of tumor cells, it couldn't lead to death of cells. Under action of Age, the proliferation of tumor cells was halted at G0/G1 stage of cell cycle, and showed no direct cytotoxic effect by Age. Age could induce lowering of the expression of Rb, Cdk2 and Cdk4, cause halt of tumor cell proliferation.</p><p><b>CONCLUSION</b>The tumor inhibitory effect of Age is realized by way of regulating the activity of cell cycle controlling enzymes to suspend the proliferation of tumor cells.</p>

Experimental study on anti-tumor effects of cortex Acanthopanacis senticosus in vivo and in vitro / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To provide a basis for development and preparation of the new anti-tumor agents from Cortex A-canthopanacis senticosus (CAS), through isolating the active substances from CAS and studying the anti-tumor effect of CAS extracts in vivo and in vitro.</p><p><b>METHODS</b>The effects of CAS extracts and its isolated ingredients on tumor cell proliferation in vitro was determined by 3H-TdR incorporation; the anti-tumor component of CAS was isolated and purified by chromatography; the tumor bearing mice model was established by injecting tumor cell subcutaneously, and the model was used to observe the anti-tumor effect of CAS extract administered through gastrogavage.</p><p><b>RESULTS</b>CAS extract showed obvious inhibition on tumor cell proliferation originated from multiple tissues (P < 0.01) and displayed a better dose-effect relationship. After orally taken CAS extract, the general condition of mice in the experimental group were better than that in the untreated control group, revealing a slower growth and significantly prolonged survival period (P < 0.01). A protein component, having inhibitory effect on tumor cell proliferation and the molecular weight was 64 kda, it was isolated by the thin layer gel chromatography.</p><p><b>CONCLUSION</b>CAS has not only the in vitro inhibitory effect on cell proliferation of multiple kinds of tumor, but also a good anti-tumor effect in vivo. The anti-tumor activity of CAS is correlated with a protein component with the molecular weight of 64 kda. Further isolation, purification, study on mechanism will provide scientific evidence for clinical application and development of CAS in anti-tumor effect.</p>

Extracorporeal experimental study on immuno-modulatory activity of Astragalus memhranaceus extract / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Astragalus membranaceus extract (AME) in regulating the immune function of human peripheral blood immune cells (PBIC) in vitro.</p><p><b>METHODS</b>Effects of AME on the proliferation activity of peripheral blood mononuclear cells (PBMC) and the tumor cell phagocytosis of peripheral blood adherent monocytes (PBAM) were measured by using 3H-TdR incorporation. Effect of the tumor-killing activity of cytotoxic T-lymphocyte (CTL) was determined by using 51Cr-releasing assay. Effects on production of IgG by peripheral blood B cells (PBBC) and IL-6 by PBAM were tested by means of ELISA, and effect on production of TNF-alpha by PBAM was studied by means of biological method. Besides, the protein elements of AME were analysed by SDS-PAGE.</p><p><b>RESULTS</b>AME could promote the proliferation of human PBMC, elevate the tumor cell-killing activity of CTL, strengthen the tumor cell phagocytosis and cytokines (TNF-alpha and IL-6) production of PBAM, and promote the IgG production of PBBC. AME contained multiple protein elements.</p><p><b>CONCLUSION</b>AME has effect in enhancing human immuno-function and anti-tumor activity, it could be applied in clinical practice for immuno-modulation and tumor treatment.</p>

Effects of cholecystokinin octapeptide on rat cardiac function and the receptor mechanism / 生理学报

The aim of this study was to explore the effects of cholecystokinin octapeptide (CCK-8) on cardiac function and the receptor mechanism in anesthetized rats. The mean arterial pressure (MAP), heart rate (HR), the left ventricle systolic pressure (LVP) and the maximal/minimum rate of LVP (+/-LV dp/dt(max)) were measured. The results obtained are as follows. (1) Low dose of CCK-8 (0. 4 microgram/kg i.v.) caused tachycardia and slight increase in MAP, LVP and LV dp/dt(max) (P<0.01), while medium dose (4.0 microgram/kg i.v.) and high dose of CCK-8 (40 microgram/kg i.v.) elicited a bradycardia and marked increase in MAP, LVP and LV dp/dtmax (P<0.01). (2) Proglumide (1.0 mg/kg i.v.), a CCK-receptor (CCK-R) antagonist, significantly inhibited the pressor effects of CCK-8, whilst it reversed the bradycardic responses (P<0.01). (3) Using reverse transcription polymerase chain reaction (RT-PCR), CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR) mRNA were expressed in myocardium of rats. The above results indicate that CCK-8 may enhance cardiac function in a dose-dependent manner and elicit a change in HR, which is likely induced by the activation of CCK-R on myocardium.