S180 Mice Research Articles

Discovery of novel benzylquinazoline molecules as p97/VCP inhibitors.

Introduction: Protein p97 is an extensively investigated AAA ATPase with various cellular activities, including cell cycle control, ubiquitin-proteasome system, autophagy, and NF-κB activation. Method: In this study, we designed, synthesized and evaluated eight novel DBeQanalogs as potential p97 inhibitors in vivo and in vitro. Results: In the p97 ATPase inhibition assay, compounds 6 and 7 showed higher potency than the known p97 inhibitors, DBeQ and CB-5083. Compounds 4-6 dramatically induced G0/G1 phase arrest in the HCT116 cells, and compound 7 arrested the cells in both G0/G1 and S phases. Western blots showed elevated levels of SQSTM/p62, ATF-4, and NF-κB in HCT116 cells with the treatment of compounds 4-7, confirming their role in inhibiting the p97 signaling pathway in cells. In addition, the IC50 of compounds 4-6 against HCT116, RPMI-8226, and s180 proliferation were 0.24-6.9µM with comparable potency as DBeQ. However, compounds 4-6 displayed low toxicity against the normal human colon cell line. Thus, compounds 6 and 7 were proved to be potential p97 inhibitors with less cytotoxicity. In vivo studies using the s180 xenograft model have demonstrated that compound 6 inhibited tumor growth, led to a significant reduction of p97 concentration in the serum and tumor, and indicated non-toxicity on the body weight and organ-to-brain weight ratios except for the spleen at the dose of 90μmol/kg/day for 10days. Furthermore, the present study indicated that compound 6 may not induce s180 mice myelosuppression often observed in the p97 inhibitors. Conclusion: Compound 6 displayed high binding affinity to p97, great p97 ATPase inhibition, selective cytotoxicity, remarkable anti-tumor effect, and upregulated safety, which improved the clinical potential of p97 inhibitors.

Oxidative stress and histopathological changes in several organs of mice injected with biogenic silver nanoparticles

The widespread use of silver nanoparticles (AgNPs) requires a study of their safety. The aim of the present study was to assess the levels of oxidative stress markers and histopathological changes in the experimental model of sarcoma S-180 of outbred mice caused by biogenic AgNPs. AgNPs were synthesized using 50% ethanol extract of Ocimum araratum leaves that was standardized for rosmarinic acid content. The effects of AgNPs were tested on chemiluminescence (ChL), malonic dialdehyde (MDA) content and activity of superoxide dismutase (SOD) in healthy and experimental model of sarcoma S-180 mice. It was shown that, under the influence of AgNPs, the intensity of ChL decreased, in contrast with control groups (with the exception of the hepatocytes of animals with transplanted sarcoma). The presence of AgNPs leads to the decrease of MDA in the tissues of healthy mice and to a slight increase of MDA content in the tumour and kidney tissues. AgNPs neutralize the activity of SOD in kidney tissue samples in animals with transplanted sarcoma, and in tumour tissue, they reduce SOD activity by three times. The results of the histological analysis indicate that AgNPs not only cause the destruction of tumour tissue but also lead to structural changes in hepatocytes and nephrons, which can affect the function of these organs. AgNPs are potential agents for antitumor therapy. Future studies are needed using biocompatible non-toxic NPs that meet the requirement for these drugs.

Discovery of DEBIC to correlate P-selectin inhibition and DNA intercalation in cancer therapy and complicated thrombosis.

Arterial thrombosis is one of the major complications of cancer and can seriously worsen the prognosis of the patients. These clinical findings encouraged this paper to correlate P-selectin inhibition and DNA intercalation in cancer therapy and complicated thrombosis. By designing and docking 12 derivatives of bisindole- 2-carboxylic acids into the active sites of P-selectin and d(CGATCG)2 9 derivatives were assigned to receive in vivo anti-tumor assay, and finally provided dimethyl 2,2'-[(2,2'-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]diacetate (DEBIC) to receive assays. DEBIC intercalated DNA and inhibited proliferation of tumor cells but not non-tumor cells. It slowed tumor growth of S180 mice at a dose of 0.36 μmol/kg, and slowed tumor growth of A549 bearing BABL/C mice at a dose of 8.9 μmol/kg. DEBIC was also found to inhibit arterial thrombosis by down regulating P-selectin effectively at a dose of 0.36 μmol/kg.

Anti-tumour effects of polysaccharide extracted from Acanthopanax senticosus and cell-mediated immunity.

Acanthopanax senticosus, also known as Siberian ginseng, is widely distributed throughout northern Asia and used in traditional Chinese medicine; it has been reported to prevent a number of diseases. However, the association between the antitumour and immunostimulatory activities of polysaccharide extracted from A. senticosus (ASPS) remains to be elucidated. The aim of the present study was to investigate the anti-tumour and immunomodulatory effects of polysaccharide extracted from ASPS on Crocker sarcoma S180, hepatic carcinoma H22 and uterine cervical carcinoma U14 tumour cell lines implanted in mice. High performance liquid chromatography, gas chromatography and infrared spectroscopy were used to analyse the monosaccharide composition of ASPS. The monosaccharide composition of ASPS (Arabic candy: Xylose: Glucose: Mannose) was 7.1:22.3:7.6:1.0. On day 0, female Kunming mice, were injected subcutaneously with 1×108 tumour cells in 0.2 ml. The inoculated mice were subsequently divided into five groups (10 mice/group) as follows: Model group, treated with normal saline; positive control group, treated with 30 mg/kg cyclophosphamide (CTX); and three treatment groups, treated with 200, 100 or 50 mg/kg ASPS. Non-inoculated mice were divided into the normal group, which was treated with normal saline, and the negative control group, which was treated with 200 mg/kg ASPS (n=10/group). CTX and ASPS were administered intragastrically once daily for 10 days. All mice were sacrificed on day 11. ASPS was observed to have an inhibitory effect on the growth of S180, H22 and U14 cells in solid and ascites tumour-bearing mice. Serum interleukin (IL)-2 and IL-12 levels were significantly increased in S180 solid tumour-bearing mice treated with 200 or 100 mg/kg ASPS compared with mice in the normal, control and model groups (P<0.05), whereas serum IL-2 and IL-12 levels were significantly decreased in the cyclophosphamide treatment group compared with the normal, control and model groups (P<0.05). No significant difference in serum levels of tumour necrosis factor-α level was observed between any groups. In S180 and U14 solid tumour-bearing mice, no significant differences in serum levels of interferon (INF)-γ level in were observed between groups; however, in H22 solid tumour-bearing mice, treatment with ASPS significantly increased serum INF-γ compared with the positive control group (P<0.05). The results may provide a basis for the potential application of ASPS in clinical treatment for cancer.

ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo.

To overcome the harmful side effects, low tolerance, and undesirable outcomes of the anticancer drugs, we used ethane-1,2-diamine to bridge antitumoral (S)-3-acetyl-4-oxo-tetrahydroindolo[2,3-a]quinolizine-6-carboxylic acid (ATIQC) and tumor-targeting d-glucuronic acid, thereby providing (6S)-3-acetyl-4-oxo-N-(2-(3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxamido)ethyl)-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carboxamide (ATIQCTPC). Atomic force microscopy images visualized, that in serum, ATIQCTPC formed particles of height <81 nm. These particles effectively avoided phagocytosis of macrophages and were stable in blood circulation. Distribution analysis indicated that ATIQCTPC accumulated and released ATIQC in the tumor tissue through a targeting manner. Thus, the antitumor and the anti-thrombotic activities of ATIQCTPC were 100-fold higher than those of ATIQC, and ATIQCTPC was able to prevent cancer patients from suffering from thrombosis. Based on the observation that ATIQCTPC decreased serum tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in S180 mice, we hypothesized that this is the mechanism that ATIQCTPC utilized to slow tumor growth. Additionally, we observed that ATIQCTPC inhibited thrombosis by decreasing serum P-selectin of thrombotic rats. The intermolecular association and the hexamerization manner of ATIQCTPC were experimentally evidenced and correlated with the formation of the nanoparticles.

Inhibition of Yuyihe Powder on Tumor Growth in Mice Models of Sarcoma 180

ObjectiveTo explore the antitumor effect of Yuyihe Powder (Yu Yi He San, YYHS) and its antitumor mechanism. MethodsAfter treatment, tumor weight, immune apparatus weight, the life span of transplanted animals, spleen lymphocyte proliferation assays, and IL-2 concentration in mouse serum were recorded or detected. ResultsYYHS showed strong antitumor ability. Compared with control group, mid-dose YYHS (1.0 g/kg) could inhibit the tumor growth, prolong the life span of S180-bearing mice to some extent, significantly increase the thymic and splenic indices of S180 mice, and strongly promote the secretion of IL-2 in blood; The inhibitory rate on tumor growth and life prolongation rate were 37.1% and 38.37%, respectively. ConclusionYYHS could not only significantly inhibit the growth of S180 cells, but also markedly prolong the survival time of S180 bearing mice. The mechanism of antitumor effect could obviously enhance immunologic function of the S180 bearing mice to inhibit the growth of S180 cells.

Protective mechanisms of purified polyphenols from pinecones of Pinus koraiensis on spleen tissues in tumor-bearing S180 mice in vivo.

The previous study evaluated the antitumor activity and the underlying mechanism of the purified polyphenols from pinecones of Pinus koraiensis (PPP-40) using a tumor-bearing S180 mice model. This study was designed to evaluate the protective effects of PPP-40 on spleen tissues of S180 mice in vivo. Pretreatment with PPP-40 (150 mg per kg BW per D) could significantly inhibit tumor growth, enhance spleen index and prevent the decline of haematological parameters of S180 mice induced by the tumor microenvironment. Moreover, the treatment with PPP-40 was shown to significantly inhibit splenocyte apoptosis by TUNEL staining and flow cytometry, characterized by the inhibition of splenocyte cycle (G0/G1) arrest, increase in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets (CD3+CD4+ and CD3+CD8+ T cells), as well as the production of T cell-related cytokines (IL-2, IL-12, and TNF-α) in splenocytes exposed to the tumor microenvironment. These effects were associated with a decrease in oxidative stress, as evidenced by the changes in the SOD, GSH-Px, GSH and MDA levels of liver and spleen tissues of S180 mice. Furthermore, the protective effect of PPP-40 on spleen tissues was deeply analyzed by detecting apoptosis-related proteins using immunohistochemistry staining. The results indicated that the protective multi-mechanisms of action also were associated with the inhibition of apoptosis through down-regulation protein expressions of Bax, caspase-9, caspase-8 caspase-3, Fas and up-regulation of the expressions of Bcl-2. These results suggested that PPP-40 is a natural antitumor agent and possesses strong immunomodulatory activities by protecting the spleen tissues of tumor-bearing S180 mice.

N-(3-hydroxymethyl-β-carboline-1-yl-ethyl- 2-yl)-l-Phe: development toward a nanoscaled antitumor drug capable of treating complicated thrombosis and inflammation.

It is well documented that the surfaces of cancer cells, activated platelets and inflammatory cells are rich in P-selectin. N-(3-hydroxymethyl-β-carboline-1-yl-ethyl-2-yl)-l-Phe (HMCEF) is a P-selectin inhibitor capable of simultaneously inhibiting thrombosis and inflammation. Based on the knowledge that P-selectin is a common target for antithrombotic, anti-inflammatory and antitumor drugs, the aim of this study article was to estimate the possibility of HMCEF as a nanoscaled antitumor drug. Images of transmission electron micro scopy, scanning electron microscopy and atomic force microscopy proved that HMCEF forms nanoparticles with a diameter of <120 nm that promote delivery in blood circulation. In vitro HMCEF intercalates into calf thymus DNA, cuts off DNA pBR22 and inhibits the proliferation of cancer cells. In vivo HMCEF dose dependently (0.2, 2 and 200 nmol/kg per day) slows tumor growth in treated S180 mice, and has a minimal effective dose of 2 nmol/kg per day. At 200 nmol/kg per day, HMCEF does not affect the liver and the kidney of the treated S180 mice, and at 20,000 nmol/kg HMCEF does not affect the liver and the kidney of the treated healthy ICR mice. HMCEF is a promising antitumor drug, which is characterized by its high safety and efficacy in the prevention of the complications of thrombosis and inflammation in patients.

Study on antitumor, antioxidant and immunoregulatory activities of the purified polyphenols from pinecone of Pinus koraiensis on tumor-bearing S180 mice in vivo

Pinecone polyphenols are bioactive dietary constituents that enhance health and help prevent and treat cancer through improving antioxidant and immunoregulatory activities. This study was designed to investigate the antitumor, antioxidant and immunoregulatory activities of the 40% ethanol eluent of polyphenols from pinecone of pinus koraiensis (PPP-40) in Sarcoma 180 (S180)-bearing mice models in vivo. The results of antitumor activity indicated that PPP-40 significantly inhibited S180 tumor growth and the dose of 150mg/kg exhibited the highest antitumor activity. Moreover, TdT-mediated dUTP nick end labeling (TUNEL) assay results further confirmed the apoptosis of S180 tumor cells. In addition, PPP-40 could obviously promote the expressions of Bax protein and inhibit the Bcl-2 protein, accordingly improve the expressions of activated Caspase-3 as well, which resulted in the activation of mitochondrial apoptotic pathway of tumor cells in S180 mice eventually. The results of antioxidant activity showed that the S180 mice treated with PPP-40 had the higher superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, the more glutathione (GSH) content, and the lower malondialdehyde (MDA) level in plasma comparing with non-treated control group. Moreover, the administration with PPP-40 (150mg/kg) significantly accelerated the proliferation of splenocytes (p<0.01) and increased the monocyte phagocytosis activity in vivo simultaneously. These results revealed that PPP-40 exerts an effective antitumor activity by activating the mitochondrial apoptotic pathway and improving the antioxidant and immunoregulatory activities.

Nanomedical strategy to prolong survival period, heighten cure rate, and lower systemic toxicity of S180 mice treated with MTX/MIT.

In spite of the usual combination form of methotrexate (MTX)/mitoxantrone (MIT) and various complex combination regimens of MTX/MIT with other anticancer drugs, the survival period, cure rate, and systemic toxicity still need to be improved. For this purpose, a nanostructured amino group-modified mesoporous silica nanoparticles (MSNN)−MTX/MIT was designed. In the preparation, the surface of mesoporous silica nanoparticles (MSNs) was modified with amino groups to form MSNN. The covalent modification of the amino groups on the surface of MSNN with MTX resulted in MSNN−MTX. The loading of MIT into the surface pores of MSNN−MTX produced nanostructured MSNN−MTX/MIT. Compared with the usual combination form (MTX/MIT), nanostructured MSNN−MTX/MIT increased the survival period greatly, heightened the cure rate to a great extent, and lowered the systemic toxicity of the treated S180 mice, significantly. These superior in vivo properties of nanostructured MSNN−MTX/MIT over the usual combination form (MTX/MIT) were correlated with the former selectively releasing MTX and MIT in tumor tissue and inside cancer cells in vitro. The chemical structure and the nanostructure of MSNN−MTX/MIT were characterized using infrared and differential scanning calorimeter spectra as well as transmission electron microscope images, respectively.

5-(Bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA): showing a strategy of designing drug to block lung metastasis of tumors.

Early metastasis is still the most recalcitrant factor in the treatment of lung cancer patients. By analyzing the structures and comparing the docking scores of the known pharmacophores, the authors of this paper designed 5-(bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA) as a promising lead compound to develop metastasis inhibitors. In vitro 5, 10, and 20 µM of BHIMHA concentration dependently inhibited the migration and invasion of A549 cells. In vivo 0.4, 2.0, and 8.9 µmol/kg of BHIMHA dose dependently inhibited the metastasis of LLC (Lewis Lung Carcinoma) toward lung. In vivo, 2 µmol/kg of BHIMHA showed additional actions of slowing the growth of the primary tumor of C57BL/6 mice and S180 mice as well as inhibiting xylene-induced ear edema of the mice. Therefore, BHIMHA simultaneously blocked tumor metastasis toward lung, slowed the primary tumor growth, and limited the inflammation. These pharmacological actions were correlated with the inhibition of PKCα and NF-κB expression.

Biological evaluation of PEG modified nanosuspensions based on human serum albumin for tumor targeted delivery of paclitaxel

Since its approval by the FDA, Abraxane™ has been established as a clinical standard of paclitaxel (PTX)-based therapy against a variety of cancers. Despite success, Abraxane™ is still limited by suboptimal biodistribution, unfavorable pharmacokinetics and chronic toxicities from chloroform used during preparation. Accordingly, a PTX-loaded nanosuspension based on human serum albumin (HSA) with PEG modifiers (PTX-PEG-HSA) has been developed to optimize the in-vivo biodistribution, pharmacokinetics and safety of PTX over traditional PTX-HSA nanosuspensions prepared using the accepted method for Abraxane™. Results of in-vivo pharmacokinetic (PK) studies indicated PTX-PEG-HSA achieved prolonged blood circulation, illustrated by an 8.8-fold and 4.8-fold increase in area-under-the-curve (AUC) of PTX over Taxol® and PTX-HSA, while the mean residence time (MRT) of PTX in PTX-PEG-HSA was increased by 3.2-fold and 1.5-fold, respectively. HSA mediated active targeting further suppressed non-specific distribution of PTX to normal tissues, which permitted enhanced antitumor efficacy in S180 mice over Taxol® and PTX-HSA. Safety of intravenously administered PTX-PEG-HSA was confirmed through lower hemolytic activity, a 2.2-fold and 1.2-fold increase in LD50 (113.4mg/kg) over Taxol® and PTX-HSA alongside the absence of local venous irritation. Studies herein suggest the therapeutic and clinical applicability of PTX-PEG-HSA for tumor specific therapy.

Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis.

Low selectivity of chemotherapy correlates with poor outcomes of cancer patients. To improve this issue, a novel agent, N-(1-[3-methoxycarbonyl-4-hydroxyphenyl]-β-carboline-3-carbonyl)-Trp-Lys-OBzl (PZL318), was reported here. The transmission electron microscopy, scanning electron microscopy, and atomic force microscopy images demonstrated that PZL318 can form nanoparticles. Fluorescent and confocal images visualized that PZL318 formed fluorescent nanoparticles capable of targeting cancer cells and tracing their interactions with cancer cells. In vitro, 40 μM of PZL318 inhibited the proliferation of tumorigenic cells, but not nontumorigenic cells. In vivo, 10 nmol/kg of PZL318 slowed the tumor growth of S180 mice and alleviated the thrombosis of ferric chloride-treated ICR mice, while 100 μmol/kg of PZL318 did not injure healthy mice and they exhibited no liver toxicity. By analyzing Fourier transform–mass spectrometry and rotating-frame Overhauser spectroscopy (ROESY) two-dimensional nuclear magnetic resonance spectra, the chemical mechanism of PZL318-forming trimers and nanoparticles was explored. By using mesoscale simulation, a nanoparticle of 3.01 nm in diameter was predicted containing 13 trimers. Scavenging free radicals, downregulating sP-selectin expression and intercalating toward DNA were correlated with the antitumor mechanism of PZL318.

A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3.

A new anticancer ligustrazine derivative, 3β-hydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methylester (T-OA, C38H58O3N2), was previously reported. It was synthesized via conjugating hepatoprotective and anticancer ingredients of traditional Chinese medicine. We found that T-OA exerted its anticancer activity by preventing the expression of nuclear transcription factor NF-κB/p65 and COX-2 in S180 mice. However, the selective cytotoxicity of T-OA on various kinds of cell lines has not been studied sufficiently. In the present study, compared with Cisplatin, T-OA was more toxic to human hepatoma cell line Bel-7402 (IC50 = 6.36 ± 1.56 µM) than other three cancer cell lines (HeLa, HT-29, BGC-823), and no toxicity was observed toward Madin–Darby canine kidney cell line MDCK (IC50 > 150 µM). The morphological changes of Bel-7402 cells demonstrated that T-OA had an apoptosis-inducing effect which had been substantiated using 4ʹ,6-diamidino-2-phenylindole (DAPI) staining, acridine orange (AO)/ethidium bromide (EB) staining, flow cytometry and mitochondrial membrane potential assay. Combining the immumohistochemical staining, we found T-OA could prevent the expression of NF-κB/p65 and COX-2 in Bel-7402 cells. Both of the proteins have been known to play roles in apoptosis and are mainly located in the nuclei. Moreover subcellular localization was performed to reveal that T-OA exerts in nuclei of Bel-7402 cells. The result was in accordance with the effects of down-regulating the expression of NF-κB/p65 and COX-2.

New synthesis method for sultone derivatives: synthesis, crystal structure and biological evaluation of S-CA.

There has been no remarkable progress in the synthesis of sultones in recent years. To facilitate more detailed studies of this functional group, we found a new method to synthesize the sulfonic acid lactone derivatives and finish its ring-closing reaction. A new sultone derivative, (E)-ethyl 4-oxo-6-styryl-3,4-dihydro-1,2-oxathiine-5-carboxylate 2,2-dioxide (S-CA), was synthesized and structurally identified by 1H-NMR, 13C-NMR, HMQC and X-ray single crystal diffraction analysis. The new rapid synthesis extended the method of ring-closing reaction of sulfonic acid lactone derivatives. The angiogenesis activities of S-CA were evaluated by the chick chorioallantoic membrane (CAM) model. It could selectively suppress small angiogenesis in CAM, without influencing either middle and large angiogenesis. In addition, anticancer efficacy of S-CA was evaluated in vivo using a murine sarcoma S180 model. Reduction of the tumor weight and tumor HE staining regions demonstrated that S-CA (10 mg/kg, intraperitoneal injection) had potent inhibition effects and a 44.71% inhibitory rate in S180 mice. Moreover, an acute toxicity test showed that the LD50 value of S-CA via intraperitoneal injection was 25.624 mg/kg.

RGDS covalently surfaced nanodiamond as a tumor targeting carrier of VEGF-siRNA: synthesis, characterization and bioassay.

A nonviral tumor targeting vector for siRNA transfer is of importance. Here, a novel delivery system consisting of a covalent conjugate of NDCO-RGDS and VEGF-siRNA, NDCO-RGDS/VEGF-siRNA, was presented. In vitro, NDCO-RGDS/VEGF-siRNA released and transferred VEGF-siRNA in a long-acting manner. Compared to the control, NDCO-RGDS/VEGF-siRNA decreased the expression of VEGF mRNA and protein in HeLa cells by 88.41 ± 3.49% and 83.94 ± 2.00%, respectively. In vivo, NDCO-RGDS/VEGF-siRNA exhibited gene silencing and slowed tumor growth. FT-MS spectrum analysis revealed that NDCO-RGDS/VEGF-siRNA mainly distributed in tumor tissue of the treated S180 mice. Therefore NDCO-RGDS could be considered a promising nonviral tumor-targeting vector for siRNA transfer in tumor therapy.

Characterization and antitumor activity of a polysaccharide from Sarcodia ceylonensis.

A water-soluble polysaccharide from Sarcodia ceylonensis was obtained by using the method of water-extraction and ethanol-precipitation. The polysaccharide was further purified by chromatography on AB-8 and ADS-7 columns, yielding a pure polysaccharide termed SCP-60. The molecular weight (Mw) of SCP-60 was calculated to be 50.0 kDa, based on the calibration curve obtained with a series of Dextran T standards. The results of FT-IR indicated that the polysaccharide contains the α-configuration of sugar units. GC-MS analysis revealed that SCP-60 was mainly composed of galactose and glucose. NMR spectroscopy revealed SCP-60 had the backbone consisting of →6)-α-Manp-(1→, α-d-Glcp-(1→, →6)-α-d-Glcp-(1→ and →6)-α-Galp-(1→. In order to evaluate the antitumor activity in vivo of the polysaccharide, a sarcoma 180 model was used. The results showed SCP-60 had strong antitumor ability, meanwhile, SCP-60 at a high dose (100 mg/kg) could significantly increase the thymic and splenic indices of S180 mice, and strongly promote the secretion of IL-2, TNF-α and IFN-γ, increase the SOD activities and reduce the concentrations of MDA in blood. Therefore the polysaccharide SCP-60 should be explored as a novel potential antitumor drug.

Immunomodulatory activity of an acidic polysaccharide isolated from Arrowhead

An acidic polysaccharide (AAP) was obtained from the aqueous extracts of the stems of arrowhead by hot water extraction followed ethanol precipitation. The immunomodulatory effect of the acidic polysaccharide (AAP) was investigated. The results showed that the high dose AAP(100 mg/ kg) has significant increased immune index of S180 mice, and strongly promoted the secretion of IL-2, TNF-α and IFN-γ. Therefore, the acidic polysaccharide AAP could be explored as a novel potential immunomodulatory drug.

Effect of Qinglongyi Polysaccharides on Complex Mobility of Erythrocytes in S180 Mice

ObjectiveTo study the effect of Qinglongyi polysaccharides (QP) in the exocarp of Juglans mandshurica on the complex mobility of erythrocytes in S180 mice. MethodsErythrocytes were collected and prepared into suspensions, and the complex mobility of cells was measured using high performance capillary electrophoresis (HPCE). Optimized experimental conditions were as follows: 50 cm × 75 μm capillary, buffer for electrophoresis; phosphate solution containing hydroxypropylmethyl cellulose (0.1 mol/L, pH 7.4), injection pressure 3.448 kPa, injection time 10 s, separation voltage 20 kV, and column temperature 25 °C. ResultsThe migration time of erythrocytes in S180 mice was longer than that in normal mice, which was 18.09 min for the model group and 12.11 min for the control group, and the complex mobility of erythrocytes in S180 mice was lower than that in normal mice, which was 0.92 × 10−4 cm2/(Vs) for the model group and 1.38 × 10−4 cm2/(Vs) for the control group. It was also found that S180 mice treated by QP could shorten the migration time and increase the complex mobility of erythrocytes. ConclusionQP could improve the complex mobility of erythrocytes in S180 mice, and HPCE could be used as a powerful tool for determining the physiological state and functions of erythrocytes.

Decreasing toxicity and synergistic effects of intracellular and extracellular polysaccharides from Phellinus igniarius to tumor-bearing mice

To study the toxicity-decreasing and synergistic effect of intracellular and extracellular polysaccharides from Phellinus igniarius on S180 mice. The PIP and PIE were extracted from the products of liquid submerged fermentation of P. igniarius. Transplanting S180 mice tumor models were established so as to observe the changes in tumor inhibiting rate, indexes of the spleen and thymus, body weight, peripheral blood cells and IFN-gamma levels when CTX was used alone and when used in combination with the PIP and PIE from P. igniarius. The results indicate that the PIP and PIE from P. igniarius can increase the activity of body immunity, attenuate the toxicity of CTX as well, and improve the anti-tumor effects.