Mouse Ascites Tumor Research Articles

Antitumor Activity of Selenium in Ehrlich Ascites Carcinoma Bearing Mice

The most common disease states of chronic liver illnesses include alcoholic liver disease (ALD), and viral hepatitis can progress to hepatocellular carcinoma (HCC). However, the role of selenium-associated tumor management angiogenesis in liver fibrosis and inflammation is yet unknown. As a result, in this current study, cytotoxicity of selenium ( Se) was evaluated against hepatocellular carcinoma cells ( HepG2) to determine IC50 ( in vitro study) and we established a mouse model of Ehrlich Ascites Carcinoma (EAC) to explore the role of selenium in the processing of tumor angiogenesis in liver injury and inflammation ( in vivo study). EAC cells was used to induce ascites tumor in albino mice and studied their consequence role on body weight gain and liver e. In EAC tumor-bearing mice, we discovered a substantial increase in body weight. Furthermore, mice with EAC tumors had higher levels of liver enzymes implicated in the etiology of liver inflammation, as well as biomarkers such as tumor necrosis factor α (TNF-), α fetoprotein (AFP), and caspase-3, Bcl2, and DNA damage.

Analysis of Cytotoxic and Antitumor Potential of Passiflora quadrangularis

ABSTRACT The cytotoxicity of ethanolic extract of Passiflora quadrangularis (PQ) leaves was analyzed on cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antitumor effect was analyzed on mouse solid and ascites tumor models. The phytochemical profile of the extract was analyzed by liquid chromatography-mass spectrometry (LC-MS). Apoptosis and cell cycle were analyzed by fluorescence resonance energy transfer (FRET) and flow cytometry. PQ exhibited cytotoxicity on Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma cells with IC50 of 9.4 and 9.2 μg mL−1 and anti-proliferative effect on breast (MCF7) and colorectal (HCT116) cancer cell lines with IC50 of 166.5 and 107.09 μg mL−1, respectively. The extract did not show toxicity in normal rat intestinal cells IEC6 and murine macrophage cells RAW264.7. In ascites tumor model, the mean survival days of the animals increased to 25 ± 4.30 d in the treated group compared to untreated (21.2 ± 2.68 d). In DLA-induced solid model, the tumor weight decreased to 1.6 ± 0.9 g from 4.5 ± 0.58 g by treatment with 400 mg kg−1 b.w. extract. LC-MS analysis revealed the presence of genistein, kaempferol, isovitexin, and quercetin that are known for anticancer potential. The acute toxicity in mice revealed that PQ is nontoxic. FRET and flow cytometry analysis indicated an induction of apoptosis in PQ-treated cells

Protective effect of aqueous extract of Pleurotus eous against Dalton's lymphoma ascites tumor in mice

The antitumor efficacy of Pleurotus eous aqueous extract (PEAE) was investigated both in vitro and in vivo. The MTT test was used to determine in vitro cytotoxicity against the Dalton's Lymphoma Ascites (DLA) cell line. PEAE's in vivo antitumor effect was compared to that of the conventional drug cyclophosphamide in a DLA-induced solid tumor model. After 24 h following DLA inoculation, experimental animals were given PEAE (500 and 1000 mg/kg bw) and cyclophosphamide (CTX, 25 mg/kg bw) orally for 30 days. PEAE was also subjected to preliminary phytochemical screening as part of the research. PEAE has a high total phenolic (9.63 GAE mg/g) and total flavonoid (3.81 CAE mg/g) content, according to phytochemical analyses. The phytochemical components of PEAE were identified by HPTLC analysis, which revealed three phenolic and one flavonoid compound peaks. PEAE exhibited antioxidant capacity, as per ABTS and FRAP assays. At 1000 μg/mL, anti-proliferative activity against the DLA cell line was moderately inhibited. PEAE reduced tumor burden in a dose-dependent way. At 500 and 1000 mg/mL PEAE treatment, there was a significant decrease in tumor volume (62.47 and 72.13%), tumor weight (53.32 and 73.72%), and improved longevity (30.89 and 58.14%). PEAE restored normal haematological and serum biochemical profiles in a dose-dependent manner, with a concurrent decrease in lipid peroxides and an increase in enzymic and non-enzymic antioxidants. Major chemical components of PEAE may be responsible for the anticancer effect, which was attributed to its enhancing endogenous mechanism, according to this study. The usefulness of PEAE as a possible naturally sourced therapeutic target for tumor prevention is emphasised.

Combined treatment with dissolved hydrogen molecule and platinum nanocolloid exerts carcinostatic/carcinocidal effects by increasing hydrogen peroxide generation and cell death in the human gastric cancer cell line NUGC-4

Many studies have shown that redox regulation is an effective therapeutic strategy for different types of cancer. We have previously demonstrated that combined treatment with dissolved hydrogen molecule (H2) and platinum nanocolloid (Pt-nc) has carcinostatic effects and that increased intracellular reactive oxygen species (ROS) levels were closely associated with carcinostatic effects in Ehrlich mouse ascites tumor cells. However, it is unknown whether combined treatment-induced ROS generation can occur in human cancer cells. Therefore, this study aimed to examine the carcinostatic effect of the combined treatment in human cells and investigate the relationship between treatment efficacy and ROS generation. H2 and Pt-nc treatment could exert cytostatic action by inhibiting the growth of human promyelocytic leukemia HL60 and human gastric adenocarcinoma-derived NUGC-4 cells; however, no effect was observed in normal human embryo fibroblast OUMS-36 cells by the temporary exposure. These findings indicate that combined treatment with H2 and Pt-nc may act selectively in tumor cells compared with normal cells. Additionally, combined treatment with H2 and Pt-nc resulted in an approximately 200-fold increase in intracellular ROS levels compared with the control, whereas the suppressive effect of tumor cell growth was abrogated entirely by catalase treatment in NUGC-4 cells. Furthermore, combined treatment with H2 and Pt-nc induced hydrogen peroxide generation, cellular morphological changes, cell death, and a decline in DNA synthesis-positive cells. In conclusion, combined treatment with H2 and Pt-nc can induce carcinostatic/carcinocidal effects through intracellular ROS increase, morphological changes, cell death, and DNA synthesis suppression in the human tumor cell line.

High-Precision Lensless Microscope on a Chip Based on In-Line Holographic Imaging.

The lensless on-chip microscope is an emerging technology in the recent decade that can realize the imaging and analysis of biological samples with a wide field-of-view without huge optical devices and any lenses. Because of its small size, low cost, and being easy to hold and operate, it can be used as an alternative tool for large microscopes in resource-poor or remote areas, which is of great significance for the diagnosis, treatment, and prevention of diseases. To improve the low-resolution characteristics of the existing lensless shadow imaging systems and to meet the high-resolution needs of point-of-care testing, here, we propose a high-precision on-chip microscope based on in-line holographic technology. We demonstrated the ability of the iterative phase recovery algorithm to recover sample information and evaluated it with image quality evaluation algorithms with or without reference. The results showed that the resolution of the holographic image after iterative phase recovery is 1.41 times that of traditional shadow imaging. Moreover, we used machine learning tools to identify and count the mixed samples of mouse ascites tumor cells and micro-particles that were iterative phase recovered. The results showed that the on-chip cell counter had high-precision counting characteristics as compared with manual counting of the microscope reference image. Therefore, the proposed high-precision lensless microscope on a chip based on in-line holographic imaging provides one promising solution for future point-of-care testing (POCT).

Antitumor Activity of the Combination of Topotecan and Tyrosyl-DNA-Phosphodiesterase 1 Inhibitor on Model Krebs-2 Mouse Ascite Carcinoma

Topotecan is a cytostatic drug from the camptothecin group, it acts by inhibiting topoisomerase 1 (TOP1). Tyrosyl-DNA phosphodiesterase 1 (TDP1) is capable of interfering with the action of TOP1 inhibitors, reducing their therapeutic efficacy. Suppression of TDP1 activity may enhance the effects of topotecan. In this work, we investigated the effect of the antitumor drug topotecan alone and in combination with a TDP1 inhibitor, a hydrazinothiazole derivative of usnic acid, on Krebs-2 mouse ascites tumors. We have previously shown that this derivative efficiently inhibits TDP1. In the present work, we show that both topotecan and the TDP1 inhibitor have an antitumor effect when evaluated separately. The combination of topotecan and the TDP1 inhibitor additively reduces both the weight of the ascites tumor and the number of cells in ascites. In mice, the TDP1 inhibitor alone or in combination with topotecan eliminated the tumor cells. After the combined intraperitoneal administration of these two compounds, we observed cells in which lipid droplets occupied almost the entire cytoplasm and the accumulation of cell detritus, which was absent in the samples collected from mice treated with each compound separately.

Apoptosis oxidative damage-mediated and antiproliferative effect of selenylated imidazo[1,2-a]pyridines on hepatocellular carcinoma HepG2 cells and in vivo.

Imidazo[1,2-a]pyridines (IP) and organoselenium compounds have been widely exploited in medicinal chemistry due to their pharmacological activities. Hepatocellular carcinoma (HCC) has few treatment options, and unfortunately, the prognosis is poor. Thus, the development of novel therapeutic drugs is urgent. The present study aimed at evaluating the antitumor mechanism of selenylated IPagainst HepG2cells and in vivo. The selenylated IP named IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2-a]pyridine) showed high cytotoxicity against HepG2 cells (half-maximalinhibitory concentration [IC50 ] = 0.03 µM) and selectivity for this tumor cell line. At nontoxic concentration, IP-Se-06decreased the protein levels of Bcl-xL and increased the levels of p53, leading to inhibition of cell proliferation and apoptosis. This compound decreased the level of extracellular signal-regulated kinase 1/2 protein and changed the levels of proteins involved in the drive of the cell cycle, tumor growth, and survival (cyclin B1, cyclin-dependent kinase 2). In addition, IP-Se-06 decreased the number of cells in the S phase. In addition, IP-Se-06 led to increased generation of reactive oxygen species, changed antioxidant defenses, and caused DNA fragmentation. Finally, IP-Se-06 significantly inhibited the growth of Ehrlich ascites tumors in mice, increased survival time, and inhibited angiogenesis. Therefore, IP-Se-06 may be an important compound regarding the development of a therapeutic drug for HCC treatment.

Green tea ameliorates the side effects of the silver nanoparticles treatment of Ehrlich ascites tumor in mice

Silver nanoparticles (AgNPs) have anti-cancer effects with fewer side effects than standard chemotherapeutic agents, however, they exert oxidative stress-based adverse effects on normal cells and so their applications have raised concern about possible health and environmental risks. We evaluated whether green tea extract (GTE), which contains potent antioxidants, could ameliorate AgNPs geno-, cyto-, and histotoxicities without decreasing their therapeutic potential against Ehrlich ascetic carcinoma (EAC). GTE enhanced the anti-cancer effect of AgNPs against EAC cells and ameliorated the genotoxic effect of AgNPs as indicated by lowering chromosomal aberrations and micronucleus frequencies. Additionally, GTE relieved most of degenerative histological changes induced by AgNPs. GTE restored the increased MDA and the decreased SOD, GPx and CAT serum levels induced by AgNPs to levels comparable to normal. The pre-treatment with GTE and AgNPs showed better improvement than the post-treatment strategy. GTE can not only ameliorate AgNPs-induced adverse effects but also improve their anti-cancer effect against EAC. So, it could be useful in the treatment of liver dysfunction associated with AgNPs.

An experimental study of Ehrlich’s ascetic carcinoma in Swiss albino mice with chemotherapy

Background: Ehrlich-Lettre ascites carcinoma (EAC) is also known as Ehrlich cell. It was originally established as an ascites tumor in mice. The current concept that cytotoxic chemotherapeutic agents are administered at a dose to the maximum a patient can tolerate before the onset of severe and even life-threatening toxicity is still in wide clinical use. This study was conducted to evaluate the response of chemotherapy in the treatment of Ehrlich’s ascetic carcinoma. The various parameters to assess the response of various therapeutic schedules were regression of tumor by decrease in body weight of mice and decrease in abdominal girth; cell count of ascetic fluid and morphological changes of tumor cells after treatment with drugs and to study the percentage viability of the cells. Materials & Methods: A mouse bearing the tumor strain was taken from our laboratory in the Department of Pathology, IPGMER, Kolkata, where the strain was being maintained serially by inoculation of malignant cells into healthy mice every 8-10 days. In our work altogether 25 mice were taken for each set of experimental work. They were divided in four groups of 5-10 mice in each group. Results: All the mice in Group III revealed extensive metastasis with haemorrhagic ascetic fluid. About 60% mice of Group IV showed metastatic but there was no haemorrhagic fluid. None of the mice of Group IV survived beyond 35 days. Group III mice survived for a maximum of 25 days. Most of them died between 2-24 days. Conclusion: With the chemotherapy there was reduced cell count and cell viability. Actinomycin D alone produced a moderate effect on tumor cells.

Implications for the Predictivity of Cell-Based Developmental Toxicity Assays Developed Two Decades Apart

Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of in-house candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.

Synthesis, Labeling and Biological Evolution of New Thiopyrano[2,3-b]Pyridine Derivatives as Potential Anticancer Agents

The new thiopyrano[2,3-b]pyridines 4-9 could be synthesized from the nicotinonitrile derivative 1. The cytotoxicity activity of the selected compounds 5, 6 and 8 was tested against MCF-7 and HCT-116 cell lines. The compound 5 (TP5) exhibited significant inhibitory activity and displayed the most potent activity, more than 6 and 8. The compound 5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent. In the light of this result, the labeled 125I-compound 5 (125I-TP5) was prepared and its cytotoxicity against ascites tumor in mice has been evaluated. The results show that compound 5 (TP5) may be potentially used as a radiopharmaceutical for tumor diagnosis when labeled with 125I.

Combined antitumor effects of P-5m octapeptide and 5-fluorouracil on a murine model of H22 hepatoma ascites.

The present study has demonstrated that P-5m octapeptide (P-5m) has therapeutic potential in metastatic human hepatocarcinoma, possibly through the modulation of matrix metalloproteinase-2 expression. The purpose of the present study was to evaluate the antitumor effect of P-5m combined with 5-fluorouracil (5-Fu) on the treatment of hepatoma 22 (H22) hepatocarcinoma malignant ascites in a mouse model. The inhibitory effect on the growth of mouse ascites tumors was monitored by measuring body weight gain, survival time, ascites volume, numbers of tumor cells, DNA synthesis and peritoneal capillary permeability analysis. The present data revealed a significant reduction in ascites volume and cell count in mice that were treated with P-5m plus 5-Fu. Furthermore, the median survival time in mice in the combination group was prolonged compared with the disease control group. Moreover, a significant reduction in the total H22 ascites cell count in mice from the combination group was observed when compared with the disease control group. P-5m plus 5-Fu was able to induce the cell cycle arrest and inhibit the peritoneal capillary permeability of the mice. To conclude, the present study indicated that P-5m may have therapeutic potential in ascites caused by hepatocellular carcinoma.

The effects of gilaburu (Viburnum opulus) juice on experimentally induced Ehrlich ascites tumor in mice.

The aim of study was to investigate anticancer effect of Viburnum opulus (VO) on Ehrlich ascites carcinoma (EAC) bearing mice that treated with different concentrations of VO. For tumor transplantation; mice were inoculated with 1 × 106 EAC cells intraperitoneally and than divided into five groups (n = 9). Two hours after inoculation; experimental groups were treated daily with VO extract at doses of 1000 mg/kg, 2000 mg/kg, 4000 mg/kg. Extracts obtained from gilaburu juice can have hinder effect on tumor cell growth. As far as we known, this is the first study about in vivo antitumoral activity of VOon Ehrlich ascites tumor model, and consequently VO extract exhibited anticancer activity against EAC-bearing mice.

Design, synthesis and antiproliferative effect of 17β-amide derivatives of 2-methoxyestradiol and their studies on pharmacokinetics

A series of 17β-amide-2-methoxyestradiol compounds were synthesized with an aim to enhance the antiproliferative effect of 2-methoxyestradiol. The antiproliferative activity of 2-methoxyestradiol analogs against human cancer cells was investigated. 2-methoxy-3-benzyloxy-17β-chloroacetamide-1,3,5(10)-triene (5e) and 2-methoxy-3-hydroxy-17β-butyramide-1,3,5(10)-triene (6c) had comparable or better antitumor activity than 2-methoxyestradiol. The elimination half-life of 6c (t1/2β=240.93min) is ten times longer than 2-ME and the area under the curve was seven times (AUC0-tmin=2068.20±315.74μgmL−1min) higher than 2-ME, respectively. Whereas 5e had similar pharmacokinetic behavior with 2-ME (t1/2β=22.28min) with a t1/2β of 29.5 min. 6c had higher blood concentration, longer actuation duration and better suppression rate against S180 mouse ascites tumor than 2-methoxyestradiol.

Aqueous extract from pecan nut [Carya illinoinensis (Wangenh) C. Koch] shell show activity against breast cancer cell line MCF-7 and Ehrlich ascites tumor in Balb-C mice

Ethnopharmacological relevanceIn Brazil many health disorders are treated with the consumption of different varieties of tea. Shell extracts of pecan nut (Carya illinoinensis), which have significant amounts of phenolic compounds in their composition, are popularly taken as tea to prevent diverse pathologies. Aim of the studyPhenolic compounds from pecan nut shell extract have been associated with diverse biological effects but the effect on tumor cells has not been reported yet. The aim of the current work was to evaluate the relationship between DNA fragmentation, cell cycle arrest and apoptosis induced by pecan nut shell extract and its antitumor activity. Materials and methodsCytotoxicity, proliferation, cell death and cell cycle were evaluated in MCF-7 cells by MTT, colony assay, differential coloring and flow cytometry assays, respectively. DNA damage effects were evaluated through intercalation into CT-DNA and plasmid DNA cleavage. Tumor growth inhibition, survival time increase, apoptosis and cell cycle arrest were assessed in Ehrlich ascites tumor in Balb/C mice. ResultsThe cytotoxic effect of pecan nut shell extracts, the induction of cell death by apoptosis and also the cell cycle arrest in MCF-7 cells have been demonstrated. The survival time in mice with Ehrlich ascites tumor increased by 67%. DNA damage was observed in the CT-DNA, plasmid DNA and comet assays. The mechanism involved in the antitumor effect of pecan nut shell extracts may be related to the activation of key proteins involved in apoptosis cell death (Bcl-XL, Bax and p53) and on the cell cycle regulation (cyclin A, cyclin B and CDK2). ConclusionsThese results were attributed to the phenolic profile of the extract, which presented compounds such as gallic, 4-hydroxybenzoic, chlorogenic, vanillic, caffeic and ellagic acid, and catechin, epicatechin, epigallocatechin and epicatechin gallate. The results indicated that pecan nut shell extracts are effective against tumor cells growth and may be considered as an alternative to the treatment of cancer.

Phenolics from Rubus fairholmianus induces cytotoxicity and apoptosis in human breast adenocarcinoma cells

Herbal medicine is an important part of health care system in most of the countries. Rubus fairholmianus is an unexplored berry in folkloric medicine. In this study, we aimed to understand the importance of R. fairholmianus in pharmaceutical industry for the development of cost-effective cancer therapeutic drugs using in vivo and in vitro analysis. Chemical characterization, antioxidant, antiproliferative and apoptosis inducing properties of R. fairholmianus root methanolic column subfraction (RFM) were investigated. The RFM displayed the presence of alpha-tocopherol, flavonol glycoside and apigenin in the chemical characterization. DPPH (2, 2-diphenyl-1-picrylhydrazyl) and ABTS (2, 2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging assays exhibited an activity of 7.56 μg/mL (IC50) and 20514.7 μM trolox equivalents/g respectively. The solid and ascites tumors in mice were reduced significantly upon 100 mg/kg RFM treatment by reducing the tumor volume (1.86 cm3), tumor weight (69%) and increasing life span (31.74 days). The morphological features of RFM treated MCF-7 cells showed the cell damage and decreased cell numbers. The viability of treated cells decreased with 67.73% at 20 μg/mL against 96.50% in untreated cells. The treated cells (20 μg/mL) resulted in a substantial decrease (p < 0.001) in cellular ATP proliferation, increased the LDH cytotoxicity, increased apoptotic cells population (33.92%) and reduced the population of viable cells (Annexin V-/PI-) (45.56%). Increased caspase 3/7 activity and cytochrome c release were also observed in treated cells. This is the first evidence about in vitro and in vivo anticancer activity of R. fairholmianus phenolics. The major phenolics such as alpha-tocopherol, flavonol glycoside, and apigenin might be the reason behind the caspase-mediated apoptosis. Further work is warranted to study the individual effects of these bioactive compounds in the induction of cell death. Due to the apoptosis inducing properties, it can be considered as an effective adjuvant therapeutic agent in clinical trials.

Ehrlich ascites tumor-bearing mice treated with aqueous ethanol plant extract from &lt;i&gt;Euphorbia tirucalli&lt;/i&gt; showed signs of systemic toxicity

Purpose: To evaluate the antitumor effect of a latex extract from Euphorbia tirucalli Linn. (Euphorbiaceae) and its toxicity. Methods: Aqueous ethanol and petroleum ether extracts were obtained through maceration. .Maximum tolerated dose was determined in healthy mice. Antitumor activity was measured in Ehrlich ascites tumor-bearing mice treated with the extract through intraperitoneal injection (62.5, 125 or 250 mg/kg) every 48 h (four doses). Efficacy was assessed by weight gain, abdominal circumference, volume of ascitic fluid and packed tumor cells, tumor cell viability and survival. Toxicity indicators were serum glucose, triglycerides, total proteins, activity of alanine and aspartate aminotransferases and mass of heart, spleen, kidney and liver. A hemolysis assay was also performed. Results: Doses of 62.5 and 125 mg/kg caused no antitumor activity, while 250 mg/kg dose reduced weight gain (3-fold), abdominal circumference and volume of ascitic fluid (> 50 %) and packed cells (50 %), but lowered tumor cell viability (40 %). However, mice treated with the extract survived for a shorter time than control mice. Furthermore, the 250 mg/kg dose caused cardiac atrophy, splenomegaly and fasting hyperglycemia. The extract caused hemolysis, and the half-maximal effective concentration (EC 50 ) was 1.6 (0.9 – 2.7) mg/mL. Conclusion: Euphorbia tirucalli extract inhibits Ehrlich ascites tumor in mice, but the therapeutic dose is also harmful to non-tumor tissues. Keywords: Euphorbia tirucalli , Ehrlich ascites tumor-bearing mice, Antitumor, Toxicity, Cardiac atrophy, Splenomegaly

Antitumor Effects of Ethanol Extracts from Hyptis Rhomboidea in H22 Tumor-bearing Mice.

Background:Research the antitumor effects of ethanol extracts from Hyptis rhomboidea in H22 tumor-bearing mice. At the fist-stage of the experiments, the research team took MTT method to measure the antitumor activity in vitro, then selected the most inhibitory tumor cell strain as the test object of antitumor activity in vivo, established three models of a solid tumor H22 liver cancer, ascites tumor, and immunodeficiency in male mice. From inflammatory factor, liver toxicity, in vivo antioxidant index to observe antitumor activity of ethanol extracts from H. rhomboidea.Materials and Methods:Hundred and twenty ICR male mice were used to establish three models of a solid tumor H22 liver cancer, ascites tumor, and immunodeficiency in male mice and models group of a solid tumor H22 liver cancer randomly divided into six groupshe normal control group, the model control group, the positive group (cyclophosphamide), the sample treated group (high - 1.300 g/kg, medium - 0.750 g/kg, low - 0.373 g/kg). The animals were sacrificed 15d after oral administration and tumors were taken out for the tumor weights and antitumor rates. Blood in eyeball was collected for the determination of aspartate transaminase, alanine transaminase, malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-2, and tumor necrosis factor (TNF)-α in serum. Sections of tumor issue were prepared, and morphological changes in tumor tissue cells were observed using hematoxylin and eosin staining technique.Results:The results showed that ethanol extracts from H. rhomboidea have a certain inhibitory effect on the digestive tumor cells. In solid tumor model, the inhibitory rate is up to 68.84% of the high dose of treated group from H. rhomboidea, and H. rhomboidea could improve the immune organ index, decrease the concentration of TNF-α and IL-2 in serum. In ascites tumor model, H. rhomboidea could slow down weight gain in mice and prolong the survival time; in immunodeficiency model, H. rhomboidea could improve the serum TNF-α and, IL-2 levels, increase SOD activity, and reduce MDA content, so as to achieve antitumor effect.Conclusions:Ethanol extracts from H. rhomboidea have obvious antitumor activity in vivo and can improve a tumor-burdened mice inflammation factors, improve the survival quality of H22 tumor mice, and enhance immunity and antitumor activity.SUMMARY Ethanol extracts from Hyptis rhomboidea have obvious antitumor activity without obviously liver damageThe experiment results prompt that the antitumor activity probably caused by decreasing the inflammatory factors, improve the survival quality, enhance the abnormal cytokines and scavenging free radicals, and raising autoimmune function in H22 tumor bearing mice. Abbreviations used: H. rhomboidea: Hyptis rhomboidea; AST: Aspartate transaminase; ALT: Alanine transaminase; MDA: Malondialdehyde; SOD: Superoxide dismutase; IL-2: Interleukin 2; TNF-α: Tumor Necrosis Factor-α; CTX: Cyclophosphamide.

Reversal effect and mechanism of Ginkgo biloba exocarp extracts in multidrug resistance of mice S180 tumor cells.

The aim of the present study was to investigate the reversal effect and its related mechanism of Ginkgo biloba exocarp extracts (GBEEs) in obtained multidrug resistance (MDR) of mice S180 tumor cells in vitro and in vivo. In order to simulate the clinical PFC [cis-dichlorodiamineplatinum, cisplatin (DDP) + fluorouracil (FU), FU+cyclophosphamide and cyclophosphamide] scheme, a gradually increasing dose was administered in a phased induction in order to induce S180 cells in vivo and to make them obtain multidrug resistance. The results in vitro demonstrated that GBEE could significantly increase the IC50 of DDP on S180 MDR cells, increase the accumulation of Adriamycin (ADR) and rhodamine 123 (Rho 123), and reduce the efflux of Rho 123 of S180 MDR cells. The results from the in vivo treatment with a combination of GBEE and DDP to S180 MDR ascites tumor in mice demonstrated that each dose of GBEE could effectively reverse the drug-resistance of S180 MDR cells to DDP in order to extend the survival time of mice with ascite tumors and inhibit tumor growth in solid tumor mice. In addition, GBEE effectively inhibited the expression of MDR-1 mRNA and multidrug resistance-associated protein-1 mRNA in S180 MDR cells of ascites tumor in mice and improved the expression levels of cytokines, including interleukin (IL)-3, IL-18 and interferon-γ in the blood serum of S180 MDR tumor-bearing mice. The present study showed that the mechanism of GBEE reversal of MDR may be associated with the inhibition of the functional activity of P-glycoprotein, the downregulation of drug resistance related gene expression of S180 MDR cells and the improvement of the production of related serum cytokines of S180 MDR tumor mice.

Digoxin is a selective modifier increasing platinum drug anticancer activity.

Using the model of breast cancer Ehrlich ascites tumor in mice, we showed that a sigle intraperitoneal injection of cardiac glycoside digoxin 1 h before the intraperitoneal injection of cisplatin increased the anticancer effect of the cytostatic drug more than twice when recalculated for the dose. It is assumed that the modifying effect of digoxin is determined by the direct inhibition of glycolysis in tumor cells. Taking into account the design of the study, we consider promising the clinical evaluation of the effectiveness of digoxin as a modifier of cisplatin efficiency in intracavitary therapy of ascites cancers with pleural and abdominal dissenmination.