Carcinoma Cells In Mice Research Articles

Effects of Simple and Angular Chromones on Tumor Cell Respiration

A set of structurally related compounds incorporating a chromone moiety as an essential component of their structures were tested against the TA3 mouse carcinoma cell line and its multidrug-resistant variant TA3-MTX-R. A tentative structure–activity relationship was found for this family of substances, suggesting that a Michael addition at C-1 is involved in the mechanism that provokes the activities.

Significance of Tumor-Associated Stroma in Promotion of Intratumoral Lymphangiogenesis: Pivotal Role of a Hyaluronan-Rich Tumor Microenvironment

Stromal cells, together with extracellular matrix components, provide a tumor microenvironment that is pivotal for cancer cell growth and progression. In our previous study using a conditional transgenic mouse model of breast cancer, the overproduction of hyaluronan, a major extracellular constituent, accelerated tumor angiogenesis through stromal cell recruitment. This finding led us to investigate the role of hyaluronan in the lymphatic vessel system. Here, we have found that microenvironmental hyaluronan promoted tumor lymphangiogenesis concurrently with the formation of stromal structures. Additionally, lymphatic vessels frequently penetrated and accumulated into stromal compartments, and up-regulation of vascular endothelial growth factor-C and -D was detected at tumor-stromal interfaces. To assess the contribution of stromal cells to lymphangiogenesis in vivo, we established tumor-associated fibroblasts from hyaluronan-overproducing mammary tumors and implanted them together with carcinoma cells from control tumors or MCF-7 human breast carcinoma cells in nude mice. Carcinoma cells grew rapidly in association with marked stromal reactions and lymphangiogenesis. Without the stromal cells, however, the tumors developed slowly with less stroma and lymphatic vessels. These findings underline the significance of tumor-associated stroma in the promotion of intratumoral lymphangiogenesis and suggest a pivotal role for the hyaluronan-rich tumor microenvironment.

Martin Evans: joint winner of 2007 Nobel Prize in medicine

Martin Evans: joint winner of 2007 Nobel Prize in medicine

Insights Into the Mechanisms Involved in Magnesium-Dependent Inhibition of Primary Tumor Growth

We have previously shown that a low Magnesium (Mg)-containing diet reversibly inhibits the growth of primary tumors that develop after the injection of Lewis lung carcinoma (LLC) cells in mice. Here we investigate some of the mechanisms responsible for the Mg-dependent regulation of tumor development by studying cell cycle regulation, tumor angiogenesis, and gene expression under Mg deficiency. The inhibition of LLC tumor growth in Mg-deficient mice is due to a direct effect of low Mg on LLC cell proliferation and to an impairment of the angiogenic switch. We also observed an increase of nitric oxide synthesis and oxidative DNA damage. Complementary DNA arrays reveal that Mg deficiency modulates tumor expression of genes involved in the control of cell cycle, stress response, proteolysis, and adhesion. Our results suggest that Mg has multiple and complex roles in tumor development.

Successful co-immunoprecipitation of Oct4 and Nanog using cross-linking

The transcription factors Oct4 and Nanog are essential for the maintenance of an undifferentiated and pluripotent state in early embryonic cells, embryonic stem cells and embryonal carcinoma cells in humans and mice. These factors are co-localized to promoters of more than 300 genes, and synergistically regulate their activities. Currently, the molecular interaction between these two factors has not been well-characterized. During attempts to co-immunoprecipitate Oct4 and Nanog we found that cross-linking with dithiobis[succinimidylpropionate] was necessary to maintain their interaction. This result was supported by gel filtration analysis. Surprisingly, formaldehyde, a cross-linker commonly used during chromatin immunoprecipitation of Oct4 and Nanog, did not preserve the complex. Our findings demonstrate the effectiveness of using DSP to mitigate the instability of the interaction between these two particular proteins. Additionally, this solution may potentially allow us to identify novel members of the Oct4–Nanog complex, leading to better understanding of the regulatory mechanisms behind pluripotency.

Effects of direct injection of dehydrated ethanol on PC3 human prostate cancer cells in nude mice: Preliminary study

The effect of direct local injection of dehydrated ethanol on hormone-independent prostatic carcinoma cells (PC3 cells) implanted in nude mice was investigated. PC3 tumors were implanted subcutaneously into 30 nude mice. Three weeks later, dehydrated ethanol was injected directly into the tumors. Twenty-three animals received an injection of ethanol at a volume of 40 microL, 80 microL, or 160 microL, and were divided into a low-dose group (n = 11) and a high-dose group (n = 12) on the basis of the ethanol/tumor volume ratio (<30% versus> or =30%). The control group (n = 7) was injected with 40 microL of physiological saline. The tumor volume before treatment was 324.9 +/- 110.9 mm(3) and was assessed as well as 1 day, 4 days, 1 week, 2 weeks, and 3 weeks after injection. Then the changes of tumor volume were compared between the two ethanol groups (low-dose group and high-dose group) and the control group. Histological examination was performed for up to 3 weeks after injection. Assessment of tumor volume showed that the ethanol/tumor volume ratio was 16.1 +/- 5.3% in the low-dose group (n = 5) and 51.8 +/- 20.3% in the high-dose group (n = 6). Tumor growth was significantly inhibited after 1 and 2 weeks in the ethanol groups compared with the control group (n = 3). After 3 weeks, there was a tendency for tumor regrowth in the low-dose group, but growth inhibition was maintained in the high-dose group. Histological examination showed tumor degeneration and necrosis with feeding vessel obstruction in the acute phase. Local injection of dehydrated ethanol regressed tumors of prostatic carcinoma cells in nude mice, with the degeneration of tumor cells and occlusion of feeding vessels.

An orthotopic floor‐of‐mouth model for locoregional growth and spread of human squamous cell carcinoma

The molecular investigation of head and neck cancer targets requires the utilization and optimization of established animal models to characterize the effects of gene transcription and protein expression on invasion and metastasis. Floor-of-the-mouth murine models have been developed to study tumor growth, invasion, and metastasis of murine squamous cell carcinoma (SCC) cells in immunocompetent mice and invasion and metastasis of human SCC cells in nude mice. However, there are tumor cell lines that do not produce tumors in mice, using standard techniques, thus reducing the utility of the model to study specific genetic or treatment conditions. Furthermore, these techniques require large tumor volumes raising the possibility of airway compromise. In this report, we detail significant modifications to the orthotopic floor-of-mouth murine model for human SCC to facilitate predictable growth of a large panel of University of Michigan SCC cell lines. Furthermore, we describe the use of bioluminescence and micro-computed tomography to monitor tumor growth and bony invasion.

The Host Inflammatory Response Promotes Liver Metastasis by Increasing Tumor Cell Arrest and Extravasation

Inflammation can play a regulatory role in cancer progression and metastasis. Previously, we have shown that metastatic tumor cells entering the liver trigger a proinflammatory response involving Kupffer cell-mediated release of tumor necrosis factor-alpha and the up-regulation of vascular endothelial cell adhesion receptors, such as E-selectin. Here, we analyzed spatio-temporal aspects of the ensuing tumor-endothelial cell interaction using human colorectal carcinoma CX-1 and murine carcinoma H-59 cells and a combination of immunohistochemistry, confocal microscopy, and three-dimensional reconstruction. E-selectin expression was evident mainly on sinusoidal vessels by 6 and 10 hours, respectively, following H-59 and CX-1 inoculation, and this corresponded to a stabilization of the number of tumor cells within the sinuses. Tumor cells arrested in E-selectin(+) vessels and appeared to flatten and traverse the vessel lining, away from sites of intense E-selectin staining. This process was evident by 8 (H-59) and 12 (CX-1) hours after inoculation, coincided with increased endothelial vascular cell adhesion molecule-1 expression, and involved tumor cell attachment in areas of intense vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 expression. Nonmetastatic (human) MIP-101 and (murine) M-27 cells induced a weaker response and could not be seen to extravasate. The results show that metastatic tumor cells can alter the hepatic microvasculature and use newly expressed endothelial cell receptors to arrest and extravasate.

Chemoimmunotherapeutic Approach to Prolonged Survival Time in Combination with Immunization and Glutamic Acid Derivatives with Antitumor Activity in Tumor-Bearing Mice

Cancer is one of the major causes of death. For cancer, the general conventional treatment and standard of care for clinical oncology remains surgery followed by radiation and/or systemic chemotherapy as deemed appropriate based on the clinical findings. Chemoimmunotherapy is an approach to treat cancer where chemotherapy is given along with immunotherapy. Chemoimmunotherapy may be useful to enhance survival time in cancer by improve immunity of the patients. This approach may enhance the therapeutic efficacy. A comparative study was done to assess the therapeutic efficacy of the whole cell vaccine and the tumor extract with or without combination chemotherapy with the synthesized glutamine and glutamic acid derivatives and analogs as well as the standard drug etoposide against Ehrlich Ascites Carcinoma (EAC) cells in Swiss Albino mice. The study showed promising results with the compound 5-N-n-hexyl-2-(4-iso-butylbenzenesulphonyl)glutamine. The compound when combined with the whole cell vaccine as well as the tumor extract increases the survival time and the therapeutic efficacy which is comparable with that of standard drug etoposide.

Alpha-tocopheryl succinate (α-TOS) influences cell vitality and enzyme activity in Ehrlich ascites carcinoma cells

Background: One of the most important strategies in research and development of new anticancer agents is the tumor-specific induction of apoptosis. The effects of semisynthetic derivative of vitamin E, (?-TOS, D-?-tocopheryl succinate), appear to be largely restricted to malignant cells. Methods: We investigated the in vivo effects of intraperitoneally administered ?-TOS on vitality of Ehrlich ascites carcinoma cells (EAC) in mice, as well as the influence of ?-TOS on specific activity of enzymes involved in antioxidative mechanisms in EAC cells. Results: According to our results, the intraperitoneal application of ?-TOS induces the decrease of the EAC vitality, and the statistically significant alteration of the glutathione-dependent enzyme activity in EAC cells. Conclusion: We may conclude that ?-TOS is an important micronutrient, with significant impact on vitality and metabolism of malignant cells.

The CXCR5 Chemokine Receptor Is Expressed by Carcinoma Cells and Promotes Growth of Colon Carcinoma in the Liver

The chemokine receptor CXCR5 is expressed by B cells and certain T cells and controls their migration into and within lymph nodes. Its ligand BCA-1/CXCL13 is present in lymph nodes and spleen and also in the liver. Surprisingly, we detected CXCR5 in several mouse and human carcinoma cell lines. CXCR5 was particularly prominent in pancreatic carcinoma cell lines and was also detected by immunohistochemistry in 7 of 18 human pancreatic carcinoma tissues. Expression in CT26 colon carcinoma was low in vitro, up-regulated in vivo, and rapidly lost when cells were explanted in vitro. CXCL13 strongly promoted proliferation of CXCR5-transfected CT26 cells in vitro. In the liver, after intrasplenic injection, these CXCR5 transfectants initially grew faster than controls, but the growth rate of control tumors accelerated later to become similar to the transfectants, likely due to the up-regulation of CXCR5. Inhibition of CXCR5 function, by trapping CXCR5 in the endoplasmic reticulum using a CXCL13-KDEL "intrakine," had no effect on initial growth of liver foci but later caused a prolonged growth arrest. In contrast, s.c. and lung tumors of CXCR5- and intrakine-transfected cells grew at similar rates as controls. We conclude that expression of CXCR5 on tumor cells promotes the growth of tumor cells in the liver and, at least for CT26 cells, seems to be required for outgrowth to large liver tumors. Given the limited expression on normal cells, CXCR5 may constitute an attractive target for therapy, particularly for pancreatic carcinoma.

Stimulation through CD40 on Mouse and Human Renal Cell Carcinomas Triggers Cytokine Production, Leukocyte Recruitment, and Antitumor Responses that Can Be Independent of Host CD40 Expression

CD40, a member of the TNFR superfamily, is expressed on a variety of host immune cells, as well as some tumors. In this study, we show that stimulation of CD40 expressed on both mouse and human renal carcinoma cells (RCCs) triggers biological effects in vitro and in vivo. Treatment of the CD40+ Renca mouse RCC tumor cells in vitro with an agonistic anti-CD40 Ab induced strong expression of the genes and proteins for GM-CSF and MCP-1, and induced potent chemotactic activity. Similarly, administration of alphaCD40 to both wild-type and CD40-/- mice bearing Renca tumors resulted in substantial amounts of TNF-alpha and MCP-1 in the serum, increased the number of total splenocytes and MHC class II+ CD11c+ leukocytes, and when combined with IFN-gamma, inhibited the progression of established Renca tumors in vivo in both wild-type and CD40-/- mice. Similarly, treatment of CD40+ A704 and ACHN human RCC lines with mouse anti-human CD40 Ab induced strong expression of genes and proteins for MCP-1, IL-8, and GM-CSF in vitro and in vivo. Finally, in SCID mice, the numbers of ACHN pulmonary metastases were dramatically reduced by treatment with species-specific human CD40 Ab. These results show that CD40 stimulation of CD40+ tumor cells can enhance immune responses and result in antitumor activity.

The Secretory Leukocyte Protease Inhibitor Is a Type 1 Insulin-Like Growth Factor Receptor–Regulated Protein that Protects against Liver Metastasis by Attenuating the Host Proinflammatory Response

The secretory leukocyte protease inhibitor (SLPI) can attenuate the host proinflammatory response by blocking nuclear factor kappaB (NF-kappaB)-mediated tumor necrosis factor alpha (TNF-alpha) production in macrophages. We have previously shown that highly metastatic human and mouse carcinoma cells, on their entry into the hepatic microcirculation, trigger a rapid host proinflammatory response by inducing TNF-alpha production in resident Kupffer cells. Using GeneChip microarray analysis, we found that in mouse Lewis lung carcinoma subclones, SLPI expression was inversely correlated with tumor cell ability to induce a proinflammatory response and metastasize to the liver and with type 1 insulin-like growth factor receptor expression levels. To establish a causal relationship between SLPI expression and the metastatic phenotype, we generated, by transfection, multiple clones of the highly metastatic subline (H-59) that overexpress SLPI. We show here that the ability of these cells to elicit a host proinflammatory response in the liver was markedly decreased, as evidenced by reduced TNF-alpha production and vascular E-selectin expression, relative to controls. Moreover, these cells formed significantly fewer hepatic metastases (up to 80% reduction) as compared with mock-transfected controls. Our findings show that SLPI can decrease the liver-metastasizing potential of carcinoma cells and that this protective effect correlates with a decrease in the production of hepatic TNF-alpha and E-selectin. They suggest that factors that attenuate the host proinflammatory response may have a therapeutic potential in the prevention of liver metastasis.

Effects of 9,10-dihydroxy-4,4-dimethyl-5,8-dihydro-1(4 H)-anthracenone derivatives on tumor cell respiration

A series of tricyclic hydroquinones, incorporating a carbonyl group in the ortho position relative to the phenol function, were tested as inhibitors of oxygen uptake against the TA3 mouse carcinoma cell line and its multidrug-resistant variant TA3-MTX-R. The title compound, which proved to be the most active one, also exhibited low micromolar dose-dependent growth inhibition of the human tumor U937 cell line (human monocytic leukemia). A tentative structure–activity relationship is proposed for these substances. A comparison between the cytotoxicities of the title compound and 4,4-dimethyl-5,8-dihydroxynaphthalene-1-one, with their activities as inhibitors of oxygen uptake by the TA3-MTX-R cell line, is presented. Also, the inhibition of oxygen uptake by 6-(4-methylpent-3-enyl)-1,4-naphthoquinone was determined and compared with its reported cytotoxicity toward P-388 (murine lymphocytic leukemia), A-549 (human lung carcinoma), HT-29 (human colon carcinoma), and MEL-28 (human melanoma) cells. The inhibition of oxygen uptake by TA3-MTX-R cells is useful as a quick test for preliminary screening of possible anticancer activity.

Efficient Inhibition of Intra-Peritoneal Tumor Growth and Dissemination of Human Ovarian Carcinoma Cells in Nude Mice by Anti-L1-Cell Adhesion Molecule Monoclonal Antibody Treatment

The L1 cell adhesion molecule is implicated in the control of proliferation, migration, and invasion of several tumor cell types in vitro. Recently, L1 overexpression was found to correlate with tumor progression of ovarian carcinoma, one of the most common causes of cancer-related deaths in gynecologic malignant diseases. To evaluate L1 as a potential target for ovarian cancer therapy, we investigated the effects of anti-L1 monoclonal antibodies (chCE7 and L1-11A) on proliferation and migration of L1-positive human SKOV3ip ovarian carcinoma cells in vitro and the therapeutic efficacy of L1-11A against i.p. SKOV3ip tumor growth in nude mice. In vitro, both anti-L1 antibodies efficiently inhibited the proliferation of SKOV3ip cells as well as other L1-expressing tumor cell lines (renal carcinoma, neuroblastoma, and colon carcinoma). On two cell lines, hyper-cross-linking of L1-11A with a secondary antibody was necessary for significant inhibition of proliferation, indicating that cross-linking of L1 is required for the antiproliferative effect. L1-negative prostate carcinoma cells were not influenced by antibody treatment. Biweekly treatment of ovarian carcinoma-bearing mice with L1-11A led to a dose-dependent and significant reduction of tumor burden (up to -63.5%) and ascites formation (up to -75%). This effect was associated with reduced proliferation within the tumors. L1-directed antibody-based inhibition of peritoneal growth and dissemination of human ovarian carcinoma cells represents important proof-of-principle for the development of a new therapy against one of the leading gynecologic malignant diseases.

Biological and molecular properties of a new αvβ3/αvβ5 integrin antagonist

Abstract The aim of the present study was to identify specific αvβ3/αvβ5 integrin antagonists active on tumor-induced angiogenesis. To this purpose, in vitro integrin-binding assays were used to screen a library of conformationally constrained bicyclic lactam Arg-Gly-Asp–containing pseudopeptides. The results identified ST1646 as a high-affinity specific ligand for αvβ3 and αvβ5 integrins with negligible interacting with α5β1 integrin. In all the assays, ST1646 was equipotent to or more potent than the well-characterized integrin antagonists c(RGDfV) and cyclo(Arg-Gly-Asp-d-Phe-[NMe]Val) (EMD121974). In the chorioallantoic membrane assay, topical administration of ST1646 was able to prevent the angiogenic responses elicited by recombinant fibroblast growth factor-2 or vascular endothelial growth factor. In addition, systemic administration of ST1646 in mice exerted a significant antiangiogenic activity on neovascularization triggered by mammary carcinoma MDA-MB435 cells implanted s.c. in a dorsal air sac via a (Millipore Filter Corporation, Bedford, MA) chamber. Moreover, ST1646 delivery via an osmotic pump inhibited the growth and vascularization of tumor xenografts originating from the injection of αvβ3/αvβ5-expressing human ovarian carcinoma cells in nude mice. In agreement with the biochemical and pharmacologic studies, Monte Carlo/Stochastic Dynamics simulation showed that the bicyclic scaffold in ST1646 forced the compound to assume a preferred conformation superimposable to the X-ray conformation of αvβ3-bound EMD121974. Accordingly, computer-docking studies indicated that the ST1646-αvβ3 integrin complex maintains the ligand-receptor distances and interactions observed in the crystalline EMD121974-αvβ3 integrin complex. Taken together, these observations indicate that ST1646 represents a dual αvβ3/αvβ5 integrin antagonist with interesting biochemical and biological features to be tested in cancer therapy.

Constitutive expression of functional CD40 on mouse renal cancer cells: Induction of Fas and Fas-mediated killing by CD40L

CD40, a member of the TNF receptor superfamily, is expressed on B cells, dendritic cells, and some tumor cells, including melanoma and bladder carcinoma. In this study, we report that both mouse and human renal carcinoma cells (RCC) also constitutively express functional CD40. Treatment of mouse RCC with CD40L induced strong expression of genes and proteins for ICAM-1 and Fas, and this expression was further enhanced by combining CD40L with IFN-γ. Similar effects were demonstrated using an agonist anti-CD40 antibody. The increased levels of Fas expression on RCC after treatment with CD40L plus IFN-γ resulted in potent killing by either FasL-positive effector cells or agonistic anti-Fas antibody. The combination of CD40L plus IFN-γ also significantly enhanced killing of RCC by tumor-specific CTL lines. Our results demonstrate that constitutively expressed CD40 is functionally active and may provide a molecular target for the development of new approaches to the treatment of RCC.

Augmentation of antitumor effects of p53 Gene therapy by combination with HDAC inhibitor

We have previously shown that the HDAC inhibitors (HDACI) activate the p53 molecule through acetylation of 320 and 373 lysine residues, up-regulate PIG3 and NOXA and induce apoptosis in cancer cells expressing wild and pseudo-wild type p53 genes (Terui T., et al., Cancer Res. 63, 8948-8954, 2003). It has also been reported that expression of the Coxackie edenovirus receptor and subsequent transfection efficiency of the adenovirus in cancer cells were enhanced by HDACI treatment. In this study, we extended these observations to explore the combination effect of adenoviral vector carrying wild type p53 (Ad-p53) gene therapy with a HDACI, sodium butyrate (SB), on xenografted human gastric cancer cells (KATO-III) and hepatocellular carcinoma cells (HuH7) in nude mice. We first confirmed an increased expression of Coxackie Adenovirus receptors with an associated increment of transgene (X-gal) expression by SB treatment in KATO-III cells. We then injected Ad-p53 into subcutaneous tumors of KATO-III and HuH7 combined with intraperitoneal administration of SB and found a significantly higher growth suppressive effect than single treatments of each. Even a complete regression of tumors was observed in three of five mice treated with this combination while with single treatment no tumor regression was observed. Tumors treated with the combination showed higher numbers of TUNEL positive cells than those treated with a single modality. Moreover, necrotic changes were more evident in tumors treated with the combination than separately, a compatible finding to the observation that vascularity revealed by CD34 staining was poorer in tumors treated with the combination than those treated with p53 gene or SB alone. This was further supported by the finding that BAI-1 (brain specific angiogenesis inihibitor-1), an inhibitor of vascularization, was induced by SB treatment in KATO-III and HuH7 cells transfected with Ad-p53. Thus SB was shown to be an efficient potentiator of p53 gene therapy for cancer.

Development of Cell-Specific Targeting Systems for Drugs and Genes

Cell-specific targeting systems for drugs and genes have been developed by using glycosylated macromolecule as a vehicle that can be selectively recognized by carbohydrate receptors. Pharmacokinetic analyses of the tissue distribution of glycosylated proteins came to the conclusion that the surface density of the sugar moiety on the protein derivative largely determines the binding affinity for the receptors and plasma lectin. Many glycosylated delivery systems have been developed and their usefulness investigated in various settings. Galactosylated polymers, when properly designed, were found to be effective in delivering prostaglandin E1 and other low-molecular-weight drugs selectively to hepatocytes. In addition, glycosylated superoxide dismutase and catalase were successfully developed with minimal loss of enzymatic activity. A simultaneous targeting of these two enzymes to liver nonparenchymal cells significantly prevented hepatic ischemia/reperfusion injury. On the other hand, galactosylated catalase, a derivative selectively delivered to hepatocytes, effectively inhibited hepatic metastasis of colon carcinoma cells in mice. Finally, hepatocyte-targeted in vivo gene transfer was achieved by synthesizing a multi-functional carrier molecule, which condenses plasmid DNA, delivering DNA to hepatocytes through recognition by asialoglycoprotein receptors, and releasing DNA from endosomes/lysosomes into cytoplasm.

Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice

To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2 and bax. A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. Resveratrol (500 mg/kg, 1,000 mg/kg and 1,500 mg/kg) was directly injected beside tumor body 6 times at an interval of 2 d. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alterations by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and PT-PCR. Resveratrol could significantly inhibit carcinoma growth when it was injected near the carcinoma. An inhibitory effect was observed in all therapeutic groups and the inhibition rate of resveratrol at the dose of 500 mg/kg, 1,000 mg/kg and 1,500 mg/kg was 10.58%, 29.68% and 39.14%, respectively. Resveratrol induced implanted tumor cells to undergo apoptosis with apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation. The inhibition rate of 0.2 mL of normal saline solution, 1,500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol, and 1 500 mg/kg resveratrol was 13.68+/-0.37%, 13.8+/-0.43%, 48.7+/-1.07%, 56.44+/-1.39% and 67+/-0.96%, respectively. The positive rate of bcl-2 protein of each group was 29.48+/-0.51%, 27.56+/-1.40%, 11.86+/-0.97%, 5.7+/-0.84% and 3.92+/-0.85%, respectively by immunohistochemical staining. The positive rate of bax protein of each group was 19.34+/-0.35%, 20.88+/-0.91%, 40.02+/-1.20%, 45.72+/-0.88% and 52.3+/-1.54%, respectively by immunohistochemical staining. The density of bcl-2 mRNA in 0.2 mL normal saline solution, 1,500 mg/kg DMSO, 500 mg/kg resveratrol, 1,000 mg/kg resveratrol, and 1,500 mg/kg resveratrol decreased progressively and the density of bax mRNA in 0.2 mL normal saline solution, 1,500 mg/kg DMSO, 500 mg/kg resveratrol, 1,000 mg/kg resveratrol, and 1,500 mg/kg increased progressively with elongation of time by RT-PCR. Resveratrol is able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated by down-regulating apoptosis-regulated gene bcl-2 and up-regulating the expression of apoptosis-regulated gene bax.