Azoxymethane-induced Colon Cancer Research Articles

Deletion of Glutathione Peroxidase-2 Inhibits Azoxymethane-Induced Colon Cancer Development

The selenoprotein glutathione peroxidase-2 (GPx2) appears to have a dual role in carcinogenesis. While it protected mice from colon cancer in a model of inflammation-triggered carcinogenesis (azoxymethane and dextran sodium sulfate treatment), it promoted growth of xenografted tumor cells. Therefore, we analyzed the effect of GPx2 in a mouse model mimicking sporadic colorectal cancer (azoxymethane-treatment only). GPx2-knockout (KO) and wild-type (WT) mice were adjusted to an either marginally deficient (−Se), adequate (+Se), or supranutritional (++Se) selenium status and were treated six times with azoxymethane (AOM) to induce tumor development. In the −Se and ++Se groups, the number of tumors was significantly lower in GPx2-KO than in respective WT mice. On the +Se diet, the number of dysplastic crypts was reduced in GPx2-KO mice. This may be explained by more basal and AOM-induced apoptotic cell death in GPx2-KO mice that eliminates damaged or pre-malignant epithelial cells. In WT dysplastic crypts GPx2 was up-regulated in comparison to normal crypts which might be an attempt to suppress apoptosis. In contrast, in the +Se groups tumor numbers were similar in both genotypes but tumor size was larger in GPx2-KO mice. The latter was associated with an inflammatory and tumor-promoting environment as obvious from infiltrated inflammatory cells in the intestinal mucosa of GPx2-KO mice even without any treatment and characterized as low-grade inflammation. In WT mice the number of tumors tended to be lowest in +Se compared to −Se and ++Se feeding indicating that selenium might delay tumorigenesis only in the adequate status. In conclusion, the role of GPx2 and presumably also of selenium depends on the cancer stage and obviously on the involvement of inflammation.

Flaxseed (Linum usitatissimum L.) and Its Total Non-digestible Fraction Influence the Expression of Genes Involved in Azoxymethane-induced Colon Cancer in Rats

The influence of flaxseed (Linum usitatissimum L.) and its total non-digestible fraction (TNDF) on the expression of genes involved in azoxymethane (AOM)-induced colon cancer in Sprague Dawley rats was analyzed. The dose used in the animal model was two tablespoons of flaxseed per day, which is the dose recommended for humans. Flaxseed significantly decreased the crypt multiplicity (10.50 ± 3.5) compared with the AOM treatment (34.00 ± 11.0), which suggests that flaxseed exhibits a preventive effect against colon cancer. Both treatments (flaxseed and TNDF) influence the overexpression of genes involved in cell cycle arrest and mitochondrial apoptosis: p53, p21, bcl-2, bax and caspase-3. Flaxseed induced the expression of p53 and p21, whereas TNDF triggered the p21-independent expression of p53. This finding suggests that both of these treatments induced cell cycle arrest. In addition, TNDF induced mitochondrial apoptosis because the TNDF + AOM group exhibited the expression of caspase-3, decreased bcl-2 expression and increased bax expression. These results suggest that the expression of the analyzed genes is associated with the presence of dietary antioxidants linked to the cell wall of flaxseed.

Sepiapterin Ameliorates Chemically Induced Murine Colitis and Azoxymethane-Induced Colon Cancer

The effects of modulating tetrahydrobiopterin (BH4) levels with a metabolic precursor, sepiapterin (SP), on dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)-induced colorectal cancer were studied. SP in the drinking water blocks DSS-induced colitis measured as decreased disease activity index (DAI), morphologic criteria, and recovery of Ca(2+)-induced contractility responses lost as a consequence of DSS treatment. SP reduces inflammatory responses measured as the decreased number of infiltrating inflammatory macrophages and neutrophils and decreased expression of proinflammatory cytokines interleukin 1β (IL-1β), IL-6, and IL-17A. High-performance liquid chromatography analyses of colonic BH4 and its oxidized derivative 7,8-dihydrobiopterin (BH2) are inconclusive although there was a trend for lower BH4:BH2 with DSS treatment that was reversed with SP. Reduction of colonic cGMP levels by DSS was reversed with SP by a mechanism sensitive to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a specific inhibitor of the NO-sensitive soluble guanylate cyclase (sGC). ODQ abrogates the protective effects of SP on colitis. This plus the finding that SP reduces DSS-enhanced protein Tyr nitration are consistent with DSS-induced uncoupling of NOS. The results agree with previous studies that demonstrated inactivation of sGC in DSS-treated animals as being important in recruitment of inflammatory cells and in altered cholinergic signaling and colon motility. SP also reduces the number of colon tumors in AOM/DSS-treated mice from 7 to 1 per unit colon length. Thus, pharmacologic modulation of BH4 with currently available drugs may provide a mechanism for alleviating some forms of colitis and potentially minimizing the potential for colorectal cancer in patients with colitis.

Grape Seeds: Ripe for Cancer Chemoprevention

A wide variety of phytochemicals, mostly flavonoids or polyphenolics, have been shown to possess anticarcinogenic activities. Among these are the grape seed proanthocyanidins (GSPs), which are the active ingredients of grape seed extract (GSE). Substantial in vitro and preclinical in vivo studies have shown the chemopreventive efficacy of GSPs against various forms of cancers in different tumor models. In this issue of the journal, Derry and colleagues show that administration of GSE in the diet reduces azoxymethane-induced colon carcinogenesis in an A/J mouse model. The results of this innovative and comprehensive study indicate that inhibition of azoxymethane-induced colon cancer by dietary GSE is mediated through the induction of apoptosis that is associated with alterations in microRNA (miRNA) and cytokine expression profiles as well as β-catenin signaling. Notably, the demonstration that miRNA expression is affected by dietary GSE suggests a novel underlying mechanism for the chemopreventive action of GSE in colon cancer and, potentially, other cancers.

Withania somnifera and its emerging anti-neoplastic effects

I read with great interest the recent article by Minhas et al. (2012). Withania may exert a number of anti-proliferative effects besides its protective role in SLE. Withaferin A and withanolide are both extracted from Withinia. Of these, withaferin A is the most potent though withanolide also exhibits growth inhibiting activity (Choudhary et al. 2010). These anti-proliferative effects are clearly seen in NCI-H460 lung cancer cell lines (Yadav et al. 2010). Similarly, when applied to lung cancer cell lines, Withania augments the anti-neoplastic effects of chemotherapeutic agents such as paclitaxel (Senthilnathan et al. 2006). Withania extracts appear to have an immunomodulatory effect and enhance paclitaxel-induced inhibition of cell proliferation. Witharin also appears to be a radio sensitizer as it increases radio sensitivity of tumors and thereby enhances the apoptotic effects of radiotherapy (Muralikrishnan et al. 2010). Withania extracts appear to inhibit proliferation in HCT-15 colon cancer cell lines. For instance, it attenuates azoxymethane-induced colon cancer by modulating the levels of immunoglobulins G, A, and M and by exerting direct anti-proliferative effects (Mathur et al. 2004). 1-oxo-5beta, 6beta-epoxy-witha-2-enolide derived from Withania root has shown efficacy in the management of ultraviolet-B-induced dermatological carcinomas (Devi et al. 1996). Withania also appears to play a role in chemoprevention of skin malignancies. For instance, extracts from Withania roots have been shown to prevent the development of 7,12-dimethylbenz[a]anthracene (DMBA)induced skin cancers (Prakash et al. 2002). The above examples clearly illustrate the anti-proliferative effects of Withania and the need for further studies in this regard.

Pomegranate (Punica granatum) Peel Extract Efficacy as a Dietary Antioxidant against Azoxymethane-Induced Colon Cancer in Rat

Functional foods include antioxidant nutrients which may protect against many human chronic diseases by combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigate the protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumors in rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly divided into 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM or injected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM and PPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After the last AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At the end of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examined microscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemical measurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci in the PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked the AOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissue homogenates. The results suggest that PPE can partially inhibit the development of colonic premalignant lesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improving the redox status of colonic cells.

A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise

ObjectiveSeveral epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some...

Histopathological and immunohistochemical study of the effect of Punica granatum extract on Azoxymethane induced colon cancer in Rats

Histopathological and immunohistochemical study of the effect of Punica granatum extract on Azoxymethane induced colon cancer in Rats

Abstract 5590: Role of estrogen receptor-beta in colitis-associated cancer

Abstract Inflammatory bowel disease has been strongly correlated with colitis-associated cancer (CAC) cases, a subtype of colorectal cancer. Previously, we demonstrated that estrogen receptor-beta (ERβ) exerted protective effects against the development of colonic precancerous lesions in the azoxymethane-induced spontaneous colon cancer in vivo model. In the present study, we investigated whether ERβ could also be protective against CAC. Estrogen receptor-β knockout (βERKO) and wild type (WT) mice were exposed to azoxymethane, followed by dextran sodium sulfate (DSS) treatment. Three days after the DSS treatment two βERKO mice died, suggesting that these mice might be more susceptible to inflammatory inducers than WT mice. Furthermore, six weeks after DSS exposure five mice from each group were sacrificed and morphology and RNA analyses of inflammation markers were performed. All βERKO mice presented polyp-like structures in the colon (3.60 ± 0.81) and greater number of cellular infiltration areas (9.00 ± 1.50), whereas only two WT mice presented polyp-like structures (2.40 ± 1.47) and fewer number of cellular infiltration areas (4.00 ± 2.02). βERKO mice showed 9.8 and 5.6 fold increase in mRNA expression of inducible-nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α), respectively, when compared to WT mice. In both βERKO and WT mice a 2.1 fold increase in cyclooxygenase-2 (COX-2) mRNA expression was observed compared to the respective negative control groups. All together these results suggest that ERβ might be protective against CAC. These data will be compared to the group of mice that will be sacrificed 15 weeks post DSS treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5590. doi:10.1158/1538-7445.AM2011-5590

The protective effect of Hizikia fusiformis on colon cancer in azoxymethane‐treated rats

Hizikia fusiformis is a seaweed rich of soluble dietary fiber and phenol compounds which are known to have protective effects on gastrointestinal cancer. In this study, we evaluated the protective efficacy of dietary Hizikia fusiformis (HF) on colon cancer induced by azoxymethane(AOM) in rats. Hizikia fusiformis was dried in low‐temperature vacuum dryer and extracted with water (80_, 2hr, 120rpm). The extract was centrifuged (8,000rpm, 10min), filter and concentrated to 5°brix, which was added into AIN‐76A diet. The animals were assigned to 4 groups: the saline + AIN‐76A diet, AOM + AIN‐76A diet, AOM + AIN‐76A diet containing 1% CF extract, AOM + AIN‐76A diet containing 2% HF extract. All rats (male, F344) except saline controls received two AOM (15mg/kg body weight) injections via subcutaneous route; once at 6 weeks of age followed by another at 7 weeks of age. The extract of Hizikia fusiformis was added in diet of respective groups from 1 week after AOM injection until sacrifice. The number of colonic aberrant crypt foci (ACF) was reduced up to 50% in groups administered HF extract, however, the difference from the concentration was not observed. The proliferating cell nuclear antigen (PCNA) index was also significantly reduced in groups administered HF extract. Our results represent that the extract of Hizikia fusiformis have protective effect on AOM induced colon cancer in rats.

Chemopreventive Effects of Dietary Canola Oil on Colon Cancer Development

Fatty acid composition of dietary fat plays a vital role in colon tumor development in animal models. Fats containing ω-6 fatty acids (e.g., corn oil) enhanced and ω-3 fatty acids (e.g., flaxseed oil) reduced chemically induced colon tumor development in rats. The objective of the present investigation was to study the effects of dietary canola oil, a source of ω-3 fatty acid on azoxymethane-induced colon cancer development in Fischer rats and compare with dietary corn oil. Dietary canola oil significantly (P < 0.05) decreased colonic tumor incidence and tumor multiplicity as compared to dietary corn oil in rats. Fatty acid analysis showed that corn oil group had higher levels of ω-6 fatty acid levels, whereas the canola oil groups exhibited higher levels of ω-3 fatty acids from the colon and serum samples of rats. For the mechanistic study, COX-2 expression in the colon samples from the canola oil group was significantly lower (P < 0.05) as compared to the corn oil group. Taken together, dietary canola oil may be chemopreventive for colon tumor development in Fischer rats as compared to possibly by increasing ω-3 fatty acid levels and decreasing COX-2 levels.

Suppression of intestinal inflammation and inflammation-driven colon cancer in mice by dietary sphingomyelin: importance of peroxisome proliferator-activated receptor γ expression

Inflammation of the gastrointestinal tract increases the risk of developing colon cancer especially in younger adults. Dietary compounds are not only associated with the etiology of inflammation and colon cancer but also in their prevention. Sphingolipid metabolites have been shown to play a role in the initiation and perpetuation of inflammatory responses. In the present study, we investigated the suppression of dextran sodium sulfate-induced colitis and azoxymethane-induced colon cancer by dietary sphingomyelin (SM) in mice that lack functional peroxisome proliferator-activated receptor γ (PPAR-γ) in intestinal epithelial and immune cells. Dietary SM decreased disease activity and colonic inflammatory lesions in mice of both genotypes but more efficiently in mice expressing PPAR-γ. The increased survival and suppression of tumor formation in the SM-fed mice appeared to be independent of PPAR-γ expression in immune and epithelial cells. Using a real-time polymerase chain reaction array, we detected an up-regulation in genes involved in Th1 (interferon γ) and Th17 (interleukin [IL]-17 and IL-23) responses despite the reduced inflammation scores. However, the genes involved in Th2 (IL-4, IL-13 and IL-13ra2) and Treg (IL-10rb) anti-inflammatory responses were up-regulated in a PPAR-γ-dependent manner. In line with the PPAR-γ dependency of our in vivo findings, treatment of RAW macrophages with sphingosine increased the PPAR-γ reporter activity. In conclusion, dietary SM modulated inflammatory responses at the early stages of the disease by activating PPAR-γ, but its anticarcinogenic effects followed a PPAR-γ-independent pattern.

Combinational Effects of Prebiotics and Soybean against Azoxymethane-Induced Colon CancerIn Vivo

Prebiotic fructans are nondigestible carbohydrates with numerous health benefits. Soybean is a rich source of phytonutrients such as isoflavones. The objective of this study was to evaluate the chemopreventive effects of prebiotics (Synergy1) and soybean meal (SM) at 5% and 10% levels alone and in combination on azoxymethane- (AOM-) induced colon carcinogenesis. After one wk of acclimatization, Fisher 344 male rats (N = 90) were randomly assigned to 9 groups (n = 10). Control rats (C) were fed AIN-93G/M. Two s/c injections of AOM were administered to rats at 7 and 8 wk of age at 16 mg/kg body weight. Rats were killed by CO2 asphyxiation at 45 wk. Tumor incidence (%) in treatment groups ranged from 40 to 75 compared to 100 in C. Results indicate that feeding prebiotics and soybean in combination significantly reduced incidence of AOM-induced colon tumors with implications for food industry in the food-product development.

Dietary Linoleic Acid and Glucose Enhances Azoxymethane-Induced Colon Cancer and Metastases via the Expression of High-Mobility Group Box 1

Objective: High-mobility group box 1 (HMGB1) was closely associated with progression and metastasis of colorectal cancer. Methods: We examined the significance of HMGB1 in causing colon carcinogenesis induced by azoxymethane (AOM) injection in Fischer 344 rats fed on a control diet (group C), a 15% linoleic acid (LA) diet (group L), a control diet with 10% glucose drink (group G), and a 15% LA diet with a 10% glucose drink (group L+G). Results: Group L+G showed the highest body weight and calorie intake. Serum and mucosal HMGB1 levels were temporally increased in all groups, while the highest levels were observed in group L+G. Mucosal HMGB1 levels were correlated with cancer multiplicity and nodal metastases. In the AOM-injected rats fed the 15% LA diet with 10% glucose drink, administration of HMGB1 antibody suppressed serum HMGB1 concentration and cancer multiplicity . Conclusion: These data suggest that dietary LA and glucose provided the synergistic effect on AOM-induced rat colon cancer through HMGB1 induction.

Germinated brown rice (GBR) reduces the incidence of aberrant crypt foci with the involvement of beta-catenin and COX-2 in azoxymethane-induced colon cancer in rats.

Chemoprevention has become an important area in cancer research due to the failure of current therapeutic modalities. Epidemiological and preclinical studies have demonstrated that nutrition plays a vital role in the etiology of cancer. This study was conducted to determine the chemopreventive effects of germinated brown rice (GBR) in rats induced with colon cancer. GBR is brown rice that has been claimed to be richer in nutrients compared to the common white rice. The male Sprague Dawley rats (6 weeks of age) were randomly divided into 5 groups: (G1) positive control (with colon cancer, unfed with GBR), (G2) fed with 2.5 g/kg of GBR (GBR (g)/weight of rat (kg)), (G3) fed with 5 g/kg of GBR, (G4) fed with 10 g/kg of GBR and (G5) negative control (without colon cancer, unfed with GBR). GBR was administered orally once daily via gavage after injection of 15 mg/kg of body weight of azoxymethane (AOM) once a week for two weeks, intraperitonially. After 8 weeks of treatment, animals were sacrificed and colons were removed. Colonic aberrant crypt foci (ACF) were evaluated histopathologically. Total number of ACF and AC, and multicrypt of ACF, and the expression of β-catenin and COX-2 reduced significantly (p < 0.05) in all the groups treated with GBR (G2, G3 and G4) compared to the control group (G1). Spearman rank correlation test showed significant positive linear relationship between total β-catenin and COX-2 score (Spearman's rho = 0.616, p = 0.0001). It is demonstrated that GBR inhibits the development of total number of ACF and AC, and multicrypt of ACF, reduces the expression of β-catenin and COX-2, and thus can be a promising dietary supplement in prevention of colon cancer.

Deer velvet supplementation decreases the grade and metastasis of azoxymethane-induced colon cancer in the male rat

Since deer velvet (DV) extract promotes angiogenesis, its ability to modulate the growth and invasiveness of colon tumours was investigated. Male Wistar rats were each given a subcutaneous injection of azoxymethane (AOM) at 15 mg/kg once a week for 3 weeks. One week following the last dose of AOM the rats received either 1 g/kg of DV delivered in a cube of raspberry gelatin or plain raspberry gelatin daily for 26 weeks. At necropsy, tumours were measured and the distance from the anus was recorded. Tissue samples were categorised according to the Astler–Coller system. The results showed that there were no significant differences in most parameters examined (i.e. body weight gain, multiplicity, tumour volume and incidence). The only statistically significant differences seen were associated with metastasis and tumour grade. Specifically, more of the tumours in the DV-treated rats were of a lower grade compared to the controls, both when all tumour sites were considered (0.91 vs. 0.66, p < 0.0001), as well as those located only in the colon (0.95 vs. 0.84, p < 0.03). Therefore, this study can confidently conclude that DV does not increase the incidence, multiplicity, metastasis or tumour volume of AOM-induced colon cancer in the rat.

Modulating effect of Withania somnifera on TCA cycle enzymes and electron transport chain in azoxymethane-induced colon cancer in mice

The aim of the present investigation was to evaluate the efficacy of Withania somnifera on tricarboxylic acid (TCA) cycle enzymes and electron transport chain in azoxymethane-induced experimental colon cancer in mice. Azoxymethane at the dose of 15 mg/kg body weight was induced intraperitoneally once in a week for 28 days. The progression in colon tumor development was correlated with the appearance of the histological biomarker and aberrant crypt foci (ACF). Azoxymethane-induced colon cancer animals were treated with 400 mg/kg body weight of W. somnifera once in a week orally for 28 days. After the experimental period, the animals were killed and analyzed for TCA cycle key enzymes, such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and α-keto glutarate dehydrogenase (α-KGDH). The modulating effect of W. somnifera on TCA cycle key enzymes and electron transport chain complexes were investigated against colon cancer induced by azoxymethane in Swiss albino mice. Decreased activities of TCA cycle key enzymes such as ICDH, SDH, MDH, and α-KGDH in colon cancer bearing animals were observed. W. somnifera administration normalized these enzyme levels in azoxymethane-induced experimental mice. These results suggested that W. somnifera is the promising chemotherapeutic agent for the treatment of colon cancer.

Immunomodulatory Effects of Withania Somnifera on Azoxymethane Induced Experimental Colon Cancer in Mice

The efficacy of Withania somnifera on immunomodulation was tested in experimental azoxymethane induced colon cancer in mice. Azoxymethane is a potential carcinogen to induce the colon cancer in Swiss albino mice. Azoxymethane 15 mg/kg body weight was injected intraperitoneally once a week for 28 days. The colon cancer was confirmed by the appearance of aberrant crypt foci (ACF) in the colons of the experimental mice. The progression in colon tumor development was correlated with the appearance of the histological biomarker and ACF. Azoxymethane induced colon cancer animals were treated with 400 mg/kg body weight of W. somnifera extract once a week for four weeks orally. After the experimental period, the animals were sacrificed and analyzed for immunocompetent cells, immune complexes and immunoglobulins. W. somnifera significantly altered the level of leucocytes, lymphocytes, neutrophils, immune complexes and immunoglobulins (Ig) A, G and M. The azoxymethane induced colon cancer and immune dysfunction was better controlled by W. somnifera. These results suggested that the immunomodulatory effects of W. somnifera could be useful in the treatment of colon cancer.

Epidermal Growth Factor Receptor Is Required for Colonic Tumor Promotion by Dietary Fat in the Azoxymethane/Dextran Sulfate Sodium Model: Roles of Transforming Growth Factor- and PTGS2

Colon cancer is a major cause of cancer deaths. Dietary factors contribute substantially to the risk of this malignancy. Western-style diets promote development of azoxymethane-induced colon cancer. Although we showed that epidermal growth factor receptors (EGFR) controlled azoxymethane tumorigenesis in standard fat conditions, the role of EGFR in tumor promotion by high dietary fat has not been examined. A/J x C57BL6/J mice with wild-type Egfr (Egfr(wt)) or loss-of-function waved-2 Egfr (Egfr(wa2)) received azoxymethane followed by standard (5% fat) or western-style (20% fat) diet. As F(1) mice were resistant to azoxymethane, we treated mice with azoxymethane followed by one cycle of inflammation-inducing dextran sulfate sodium to induce tumorigenesis. Mice were sacrificed 12 weeks after dextran sulfate sodium. Tumors were graded for histology and assessed for EGFR ligands and proto-oncogenes by immunostaining, Western blotting, and real-time PCR. Egfr(wt) mice gained significantly more weight and had exaggerated insulin resistance compared with Egfr(wa2) mice on high-fat diet. Dietary fat promoted tumor incidence (71.2% versus 36.7%; P < 0.05) and cancer incidence (43.9% versus 16.7%; P < 0.05) only in Egfr(wt) mice. The lipid-rich diet also significantly increased tumor and cancer multiplicity only in Egfr(wt) mice. In tumors, dietary fat and Egfr(wt) upregulated transforming growth factor-alpha, amphiregulin, CTNNB1, MYC, and CCND1, whereas PTGS2 was only increased in Egfr(wt) mice and further upregulated by dietary fat. Notably, dietary fat increased transforming growth factor-alpha in normal colon. EGFR is required for dietary fat-induced weight gain and tumor promotion. EGFR-dependent increases in receptor ligands and PTGS2 likely drive diet-related tumor promotion.

A Comparison of Rice Bran, Corn Oil and Soybean Oil Against Azoxymethane Induced Colon Cancer in a Fisher 344 Rat Model

A Comparison of Rice Bran, Corn Oil and Soybean Oil Against Azoxymethane Induced Colon Cancer in a Fisher 344 Rat Model