The antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo

To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-（2,3-dibromo-4,5-dihydroxybenzyl）-2,3-dibromo-4,5-dihydroxy benzyl methyl ether （1）, （＋）-3-（2,3-dibromo-4,5-dihydroxyphenyl）-4-bromo-5,6-dihydroxy-1,3- dihydroisobenzofuran （2）, 3-bromo-4-（2,3-dibromo-4,5-dihydroxybenzyl）-5-methoxymethyl-pyrocatechol （3）, 2,2＇,3,3＇-tetrabromo-4,4＇,5,5＇-tetrahydroxy-diphenylmethane （4）, bis（2,3-dibromo-4,5-dihydroxybenzyl） ether （5）, 2,2＇,3-tribromo-3＇,4,4＇,5-tetrahydroxy-6＇-ethyloxymethyldiphenylmethane （6） were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTF assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Be17402 and HCT-8. Their inhibitory activity against protein tyrosine kinase （PTK） with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana （EELN） was evaluated on S180-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 pg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4% respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.

Inhibitory effect of acetylshikonin on human gastric carcinoma cell line SGC-7901 in vitro and in vivo

AIM:To investigate the inhibitory effect of acetylshikonin on human gastric carcinoma cell line SGC-7901 and its mechanism. METHODS:MTT assay was used to assess the inhibitory effect of acetylshikonin on proliferation of SGC-7901 cells.Apopt osis-inducing effect was determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling with Hoechst staining.Expression of mRNA and protein in Bcl-2 and Bax was analyzed by reverse transcription-polymerase chain reaction and Western blot.Antitumor effect of acetylshikonin on a mouse SGC-7901 model was also determined. RESULTS:Forty-eight hours after treatment with acetylshikonin,MTT assay showed that acetylshikonin inhibited the proliferation of SGC-7901 cells in a dose-dependent manner.The half maximal inhibitory concentration of acetylshikonin to SGC-7901 cells was 0.428±0.07 mg/L.Cell shrinkage,nuclear pyknosis and chromatin condensation,which are the characteristics of cell apoptosis,were observed in treated SGC-7901 cells and the percentage of apoptosis increased in a dose-dependent manner.Acetylshikonin downregulated the expression of Bcl-2 and up-regulated the expression of Bax in the treated SGC-7901 cells compared with the controls.The experiment in vivo showed that 0.5,1,and 2 mg/kg of acetylshikonin significantly inhibited the growth of tumor in the mouse SGC-7901 model,with an inhibitory rate of 25.00%-55.76%. CONCLUSION:Acetylshikonin inhibits the growth of SGC-7901 cells in vitro and in vivo by inducing cell apoptosis.

Purification,structural elucidation,and in vitro antitumor effects of novel polysaccharides from Bangia fuscopurpurea

A water-soluble polysaccharide,designated BFP-3,was isolated from Bangia fuscopurpurea by hot water extraction,anion-exchange,and size-exclusion chromatography and tested to determine its antitumor activity.The structural characteristics of BFP-3 were investigated by chemical and spectroscopic methods,including partial acid hydrolysis,methylation analysis,one-and two-dimensional nuclear magnetic resonance,and gas chromatography-mass spectrometry.The results showed that BFP-3 was mainly comprised of rhamnose,arabinose,mannose,glucose,and galactose.Moreover,the weight-average molecular weight of BFP-3 was estimated to be approximately 333 kDa.The backbone of BFP-3 was primarily composed of repeating 5-α-l-Araf-1→(4-α-d-Glcp-1)_(4)→4,6-β-d-Manp-1 units,and the side chains consisted of repeatingβ-d-Galp-1→(4-β-d-Galp-1)_(4)→4,6-β-d-Galp-1→3,4-α-l-Rhap,β-l-Arap-1→(3-β-d-Galp-1)_(3),andβ-l-Arap-1 units.Counting Kit-8 assays revealed that BFP-3 significantly inhibited the proliferation of A2780,COC1,SKOV3,HO-8910,and OVCAR3 ovarian cancer cells in vitro,indicating that BFP-3 could have potential applications in the treatment of ovarian cancer.

Study on the Antitumor Effects of Low-energy Laser Irradiation Combined with Cyclophosphamide

Systematic experiments about the antitumor effects of low energy laser irradiation combined with the traditional antitumor medicine of cyclophosphamide were conducted using the experimental model of mouse S180 ascites sarcoma.The three groups of tumor bearing mice were irradiated upon the inner corners with the dosages of 11 00,14 67 and 22 00 J·cm -2 LELI respectively,and injected with CYT intraperitoneally to observe the changes of the survival time,the ascites growth speed,and the kinetic changes of immune functions.The survival times of the three groups of CYT/LELI combination were obviously longer than those of the tumor and CYT control groups.Correspondingly,the amounts of ascites,tumor cells densities and total tumor cells in CYT/LELI groups decreased significantly,while the death ratio of the tumor cells increased.Comparatively,the group of 22 00 J·cm -2 LELI combined with CYT showed the most ideal antitumor effects,and the life prolongation ratio was up to 53 20%.

Studies on the Effects of Deltamethrin on Sodium Net Transport Through the in vivo Amphibian Skin

The action of micromolar concentrations of Deltamethrin on sodium net transport through the in vivo skin of the South American toad Bufo arenarum was studied. The effect of pure ethanolic insecticide solutions and commercial formulations when applied on the mucosal surface was assayed. Deltamethrin provoked a concentration-independent inhibition; the highest inhibition was found at the lowest concentrations. At highest concentrations of the insecticide the J Na was not altered

THE SPECIFIC PHOTODYNAMIC EFFECTS OF MONOCLONAL ANTIBODIES CONJUGATED WITH HEMATOPORPHYRIN DERIVATIVE ON GASTRIC CANCER IN VITRO AND IN VIVO

Murine monoclonal antibody (MoAb) BB4.3, raised against the human gastric cancer cell line BGC823, was puriffied with Protein A-Sepharose CL-4B affinity chromatography and identified as IgG2a. It was then conjugated with a hematoporphyrin derivative (HPD) by using carbodiimide. The qualitative analysis of this conjugate showed that the amount of free HPD was negligible and there were no IgG aggregates among the conjugates. The conjugate retained both the antibody and photochemical activity of HPD.In vitro, the phototoxic effect of this HPD-BB4.3 conjugate on target cells was about 15 times higher than that of free HPD. The quality of selective photocytotoxicity was proven by the greater cytotoxi-city this conjugate showed than that of corresponding normal mouse IgG (NIgG) conjugated with HPD. It showed less cytotoxicity to colon cancer cell line B-80 (negative reaction to MoAb BB4.3) than to BGC825. Moreover, its cytotoxicity to BGC823 cells could be blocked specifically by excess BB4.3 antibody, but not by another MoAb 3G9, which combines with BGC823 at different binding sites from MoAb BB4.3.Nude mice inoculated with 2 × 10- BGC823 cells were given HPD-BB4.3, HPD, HPD-NIgG, HPD plus BB4.3 and PBS, respectively then exposed to light. Four out of six animals treated with the HPD-BB4.3 conjugate remained tumor-free for a long period. Although two developed tumors, there was a significant difference between the HPD-BB4.3-treated group and all the control groups in tumor induction time, tumor growth rate, and survival time (p<0.001). The HPD-BB4.3 conjugate inhibited the growth of established tumors by more than 40% in comparison with control groups (p<0.05).

Time and Dose-related Effects of the Pyrethroid Fluvalinate on Haemolymph Carbohydrates and Gut Lipids of Honeybees,Following in vivo Injection of very Low Doses

The injection to emerging adult workerbees with fluvalinate doses ranging from 1 femtomol to 1 nanomol per individual resulted in a reduction of haemolymph carbohydrate concentrations, particularly at the lowest dose 1 hour after injections. At the same time, a large increase was observed for triacylglycerols and to a much lesser extent for steroids and phospholipids with 0.1 picomol per bee. By contrast, fatty acids, steroids and triacylglycerols exhibited a depress at the higher dose. Most responses were thus biphasic, showing that much attention should be paid to the effects of very low doses of pesticide.

ANTITUMOR EFFECTS OF WICK OF SUN-FLOWER STEM IN MICE

A well-known Chinese traditional drug, decoction of wick of sun-flower stem, has been used to treat cancer and certain other diseases.1,2 Animal experiments in mice showed that transplantation of Sarcoma 180 (S180) and of Uterus cervical cancer 14 (U14) were signlflcanly inhibited by this decoction. The Inhibition rates of tumor weight were 33 -81 % and in about 6 - 20% of treated mice, complete tumor regression has been demonstrated. So tar no acute toxic side-effect was noted. This is in contrast to most of the antitumor chemltherapeutic drugs known to produce different degrees of toxlcity or induce Immunosuppression as a side effect. For this reason, we have undertaken the present study.

ANTITUMOR EFFECT OF ACTINIDIA CHINENSIS POLYSACCHARIDE ON MURINE TUMOR

A new polysaccharide compound (ACPS-R) has recently been isolated from the root of Actinidia Chinensis Planch. When given inttaperitoneally to the transplantable tumor bearing mice at dose of 75-125 mg/kg, the tumor inhibition rate was more than 88.8% in Ehrilich ascitic cancer (EAC) or ascitic from of hepatoma (HepA) and more than 49.6% in solid hepatoma (HepS). The treatment effect of ACPS-R on EAC at dose of 80-100 mg kg and 125 mg/kg were comparable to that of cyclophosphamide at dose of 15 mg/kg and 22.5 mg/kg, respectively. ACPS-R could also prolong the life of EAC- or P388-bearing mice, and increase the percentage of EAC-free mice. In addition, when ACPS-R was used in combination with 5-Fu, the antitumor effect was enhanced as compared with 5-Fu alone. A marked increase in cAMP levels end cAMP cGMP ratio of spleen of EAC-bearing mice were observed after treatment of ACPS-R. The increase of both para meters nearly reached the normal levels of healthy mice. The increases of cAMP, cAMP cGMP and tumor remission had statistical significance. It showed an intermediate inhibitory effect of ACPS-R on DNA synthesis by incorporating 3H-TdR into EAC cells.The results indicated that ACPS-R acts as a new antitumor polysaccharide, and the treatment effect of Actinidia root in folk medicine is probably related to ACPS-R.

Sublethal Effects of the Formamidine Amitraz on Honeybees Gut Lipids, Following in vivo Injections

The time-course and dose-related action of amitraz (AMZ) on gut lipids of worker honeybees were examined over 3 hours following in vivo injections of 0.25, 0.5, 1 and 2 nmols of pesticide per bee. Significant decreases were observed at 30-45 min with 0.25 nmols per bee, for phospholipids, fatty acids, steroids and triacylglycerols. However increases were observed either later or with higher doses. The decreasing action observed with 0.25 nmol AMZ per bee was inhibited by simultaneous injections of the a antagonist phentolamine (from 0.25 to 2.0 nmols per bee). The toxicity of AMZ to honeybees thus likely involves the mobilization of lipids from the gut, via action of this formamidine pesticide on a-adrenoceptors.

The Effects of Dietary Restriction and Aging on in Vivo and in Vitro Binding of Aflatoxin B_1 to Cellular DNA

Laboratory animals maintained on a reduced calorie but nutritionally adequate diet have extended life spans and lowered incidences of spontaneous and chemically induced cancers compared to ad libitum- fed counterparts. Many of the effects of dietary restriction on laboratory animals have been suggested to be related to a deceleration of the aging process. The inhibition of age-related changes in xenobiotic metabolizing enzyme activities by dietary restriction has previously been reported. Alterations of these enzyme activities may cause changes in metabolic activation of carcinogens and, therefore, carcinogen-DNA binding. DNA-repair capability has also been reported to be enhanced in diet-restricted rats. Using AFB1 as a model carcinogen, we have studied in vivo and in vitro hepatic AFB1 -DNA binding, demonstrating that dietary restriction (60% of ad libitum consumption) may decrease the metabolic activation of AFB1, and subsequently reduce AFB 1-DNA binding. Our preliminary results obtained from the AFB 1-DNA binding experiments in isolated hepatocytes suggest that the observed age-dependent reduction in AFB 1-DNA binding which may be attributed to a loss of metabolic activating capability was delayed in the diet-restricted rats.

Effect of temsirolimus on bladder cancer cells in vitro and in vivo

Objective To examine the effects of temsirolimus, an inhibitor of mammalian target of rapamycin,on bladder cancer cell lines T24 and BIU-87 in vitro and in vivo for purpose of evaluating the probability of mTOR targeted therapy for bladder cancer. Methods After

Systematic literature review of the antitumor effect of octreotide in neuroendocrine tumors

AIM To provide a comprehensive examination of the existing evidence of the antitumor effect of long-acting octreotide in neuroendocrine tumors(NETs).METHODS A systematic literature review of clinical trials and observational studies was conducted in PubM ed, EMBASE, and Cochrane through January 18, 2017. Conference abstracts for 2015 and 2016 from 5 scientific meetings were also searched.RESULTS Of 41 articles/abstracts identified, 13 unique studies compared octreotide with active or no treatment. Two of the 13 studies were clinical trials; the remaining were observational studies. The phase 3 Placebo-Controlled, Double-Blind, Prospective, Randomized Study of the Effect of Octreotide long-acting repeatable(LAR) in the Control of Tumor Growth in Patients with MetastaticNeuroendocrine Midgut Tumors clinical trial showed that long-acting octreotide significantly prolonged time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs; no statistically significant difference in overall survival(OS) was observed, possibly due to the crossover of placebo patients to octreotide. Retrospective observational studies found that long-acting octreotide use was associated with significantly longer OS than no octreotide use for patients with distant metastases although not for those with local/regional disease. CONCLUSION The clinical trial and observational studies with informative evidence support long-acting octreotide's antitumor effect on time to tumor progression and OS. This review showed the rarity of existing studies assessing octreotide's antitumor effect and recommends that future research is warranted.

Effect of photodynamic therapy with(17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt on pancreatic cancer cells in vitro and in vivo

AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.

Suicide gene therapy of hepatocellular carcinoma and delivery procedure and route of therapeutic gene in vivo

Objective: To study the induction of sensitivity toganciclovir (GCV) or acyclovir (ACV) in humanhepatocellular carcinoma (HCC) cell line trans-ferred by an Epstein-Barr virus (EBV)-based repli-con expression vector carrying the herpes simplex vi-rus thymidine kinase (HSV-tk) gene, including kill-ing and "bystander" effect, and also the gene delive-ry procedure and route of gene therapy in vivo forHCC.Methods: Liposome-entrapped plasmid pDR2/tk wastransferred into HCC cells, and then different con-centrations of GCV or ACV were added. The trans-ferred cells were mixed with untransferred HCC cellsin different proportion and 200 μmol/L GCV wasthen added into each well. After 72 hours, all sam-ples were measured by MTT colorimetric assay. AnEBV-based plasmid eukarotic expression vector car-rying IL-2 cDNA was used. Three models of gene di-rect injection in the local liver, injection through theportal vein, and injection through the embolized he-patic artery were established in closed Wister rats.For each model, two subgroups, injected either na-ked plasmid DNA or lipofectin-plasmid complex wereincluded. The expression of the IL-2 gene was regu-larly examined immunohistochemically.Results: GCV or ACV could apparently kill thetransferred HCC cells at a concentration of 0. 2μmol/L. The inhibition rate was changed with dif-ferent drug concentrations. The "bystander" effectwas obviously induced at a transferred to untrans-ferred HCC cells ratio of 1:5. IL-2 gene expressionwas observed in liver cells of all animals on day 3,which reached peak within 3-7 days, and declined af-ter day 7. Injection of naked plasmid DNA throughthe hepatic artery plus embolization obtained a bestexpression.Conclusions: EBV-based vector is suitable for carry-ing suicide gene therapy for hepatocellular carcino-ma. Gene direct delivery in vivo combined with in-terventional surgery can be used to treat hepatocellu-lar carcinoma.

Enhancement of Antitumor Effect of Tegafur/Uracil(UFT) plus Leucovorin by Combined Treatment with Protein-Bound Polysaccharide,PSK,in Mouse Models

We evaluated the antitumor effect of combined therapy with tegafur/uracil （UFT） plus leucovorin （LV） （UFT/LV） and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly. UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

Antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” and chemotherapy on transplanted animal hepatocarcinoma

AIM： To investigate the antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” （recipe for invigorating the kidney, removing blood stasis and toxic substances） and chemotherapy on mice hepatocarcinoma. METHODS： Bushen huayu jiedu recipe （BSHYJDR） consisting of Chinese Cassia Bark, Psoralea, Zedoary, Rhubarb, etc. is equal to 1.5 g/mL liquid of originated herbs after being decoded, filtered, and concentrated. Kunming mice, weighing 18-22 g, were injected with 0.2 mL ascitic hepatocarcinoma H22 containing 1 × 10^7 cells/mL into armpit of the right forelimb of mice. After 24 h, the mice were weighed and randomly divided into tumor-bearing model control group, cisplatin （DDP） group, BSHYJDR high dosage group, low dosage BSHYJDR group, DDP combined with high and low dosage BSHYJDR group, 10 mice in each group. DDP group received injection intraperitoneally （ip） at the dosage of 1 mg/kg （equal to 1/10 LD50）, once a day for 4 d. High and low dosage BSHYJDR groups received intragastric BSHYJDR at the dosages of 26.6 and 13.3 g/kg （20 and 10 times each of clinical adult dosage） respectively, while tumor-bearing model group received the equal volume of distilled water once a day for 10 d. On the 11^th d, the mice were weighed and killed, then the tumor was dissected and weighed, the repression rate （RR） was calculated according to the mean weight of tumor （MWT）. RESULTS： Compared to the model group （MWT： 1.30±0.73）, DDP group （MWT： 0.41±0.09, RR： 68.46%） had a significant difference in the inhibition of hepatocarcinoma H22 （P〈0.01）. High dosage BSHYJDR group （MWT： 0.69±0.29, RR： 46.92%） also had a significant difference in inhibition （P〈0.05）, while no difference was found in low dosage BSHYJDR group （MVVT： 0.85±0.34, RR： 34.62%） （P〉0.05）. When DDP was combined with high dosage BSHYJDR （MWT： 0.29±0.17, RR： 77.69%） and low dosage BSHYJDR （MWT： 0.38±0.21, RR： 70.77%） respectively, we could see improvement of the inhibition effect of DDP on transplanted hepatocarcinoma H22. DDP combined with high dosage BSHYJDR had a significant difference （P〈0.001） compared to DDP, while DDP combined with low dosage BSHYJDR only had a little improvement that is not remarkable. CONCLUSION： Chinese medicine BSHYJDR in combination with chemotherapy can inhibit transplanted hepatocarcinorna in mice.

In vitro antitumor effect of cucurbitacin E on human lung cancer cell line and its molecular mechanism

Cucurbitacin E(CuE) is previously reported to exhibit antitumor effect by several means.In this study, CuE acted as a tyrosine kinase inhibitor interfering with the epidermal growth factor receptor/mitogen-activated protein kinase(EGFR/MAPK) signaling pathway and subsequently induced apoptosis and cell cycle arrest in non-small-cell lung cancer(NSCLC) cell line A549.The apoptosis regulators, cleaved Caspases-3 and Caspases-9, were observed to be increased with the treatment of CuE.The activated transcription factor STAT3 and the apoptosis inhibitor protein survivin were also observed to be reduced.The cell cycle regulators, CyclinA2, cylinB1, CyclinD1 and CyclinE, were also investigated and the results suggested that the cell cycle was arrested at G1/G0 phase.Treatment of CuE also altered the existence status of most of the participants in the EGFR/MAPK signaling.Phosphorylation of EGFR enhanced significantly, leading to the alteration of members downstream, either total amount or phosphorylation level, notably,MEK1/2 and ERK1/2.Moreover, the results of molecular simulation brought an insight on the interaction mechanism between CuE and EGFR.In summary, CuE exhibited anti-proliferative effect against A549 cells by targeting the EGFR/MAPK signaling pathway.

Antitumor Effects of Ethanol Extract from Ventilago leiocarpa Benth on Sarcoma 180 Tumor-Bearing Mice and Possible Immune Mechanism

Objective To explore the antitumor effects of ethanol extract from Ventilago leiocarpa Benth(EEVLB)on sarcoma 180(S180)tumor-bearing mice and the potential mechanism.Methods Sixty mice were randomly assigned to 6 groups according to a random number table:normal group,model group,5-fluorouracil(5-FU)group(0.02 g·kg^(−1)),and high-,medium-,low-dose EEVLB groups(100,84,and 56 g of raw material·kg^(−1)body weight,respectively),with 10 mice each group.All treatments were given once daily for 10 consecutive days.Effects of EEVLB on inhibiting tumor growth and immune function in mice were evaluated among all groups after the treatments by detecting tumor inhibition rate,organ index,serum levels of interleukin(IL)-2,-6,-10,CD3^(+)CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)ratio,caspase-3 and Bcl-2.Results EEVLB with different concentrations achieved inhibition of tumor growth in vivo,wherein the high-dose group showed the most significant reduction in tumor weight and increased apoptosis of tumor cells(P<0.05).In addition,both net weight gain and spleen index of mice showed uptrend in EEVLB treatment groups(P<0.05).Besides,serum levels of IL-2 and IL-6,percentages of CD3^(+)CD4^(+)T lymphocytes and ratio of CD4^(+)/CD8^(+)in peripheral blood were elevated in high-and medium-dose EEVLB groups compared with the model group(P<0.05).Also,upregulation of caspase-3 and downregulation of Bcl-2 were observed at protein levels in the high-dose EEVLB group(P<0.01).Conclusions EEVLB exhibits promising antitumor activity in vivo.This effect might be due to activation of apoptotic signaling pathway,increase of cytokine levels and enhancement of immune function in tumor-bearing mice.

PLASMID VACCINE ENCODING HN GENE FROM NEWCASTLE DISEASE VIRUS HAS MARKED ANTITUMORAL EFFECT IN VITRO

Objective: To explore the antitumor effects of hemaagglutinin-neuraminase gene (HN gene) from Newcastle disease virus. Methods: Plasmid vaccine of pIRHN was constructed and transfected into HeLa cells. The expression of HN was analyzed by Western blot analysis, and the mode of cell death was detected by fluorescence microscope, gel electrophoresis and TUNEL assay and the expression of p53 and bcl-2 was also analyzed in transfected Hela cells. The effect of pIRHN on sialic acid contents in the Hela cell was examined. Results: pIRHN nucleic acid vaccines could be expressed in eukaryotic cell. pIRHN could induce apoptosis after HeLa cells were transfected. The effect of antitumor responses of pIRHN was correlated with the contents of sialic acid in tumor cells, and there was no prominent evidence for the relatedness of the antitumor effect with the expression of p53 and bcl-2. Conclusion: pIRHN may become a new antitumor biological agent.