Immune Function In Tumor-bearing Mice Research Articles

Enhancement of antitumor response of staphylococcal enterotoxin C2 mutant 2M-118 by promoting cell-mediated antitumor immunity

BackgroundStaphylococcal enterotoxin C2 (SEC2) is used as an immunotherapeutic drug in China. However, SEC2 are limited due to its immunosuppressive and toxic effects. A SEC2 2M-118 (H118A/T20L/G22E) mutant generated by site-directed mutagenesis was studied to elucidate the underlying antitumor mechanism. MethodsThe effects of 2M-118 on mouse fibrosarcoma (Meth-A) cells and cytokine responses were tested in vitro using a transwell assay and ELISA, respectively. 2M-118 effect on immune function in tumor-bearing mice was tested. Cytokine levels and antitumor responses were measured using ELISA and flow cytometry, respectively. TUNEL staining and immunohistochemistry were employed to detect the tumor apoptosis and CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in tumor tissue. Results2M-118 demonstrated the growth inhibition on tumor cells, increase of cytokines production (IL-2, IFN-γ, and TNF-α) and splenocyte proliferation in vitro. 2M-118 effectively inhibited tumor development and increased lymphocytes and cytokines in a tumor-bearing mouse model. Additionally, 2M-118 regulated the tumormicroenvironment by reducing the number of myeloid-derived suppressor cells (MDSCs), increasing the number of TILs, and inducing tumorcell apoptosis. Conclusion2M-118 promotes immune function and enhances antitumor response. This indicates that 2M-118 could potentially be developed as a novel anti-tumor drug with-highefficiencyandlowtoxicity.

The Efficacy of Fosbretabulin Disodium Combined with Radiofrequency Ablation in Lung Cancer.

Radiofrequency ablation (RFA) is a technology that uses radiofrequency thermal effect to induce coagulation necrosis of tumor tissue under the guidance of imaging. However, distant metastasis of tumor cells caused by tumor angiogenesis can lead to incomplete tumor clearing. In this study, LLC1 cell line was used for the construction of subcutaneous xenografts. Either 10 mg/kg or 20 mg/kg Fosbretabulin disodium (FBTD) was intragastrically administered every 2 days for a week. RFA was performed at the end of medication. The proportion of T cells was examined by flow cytometry. Serum IgG and IgA levels of mice were examined by ELISA. Expression of certain genes was estimated by qRT-PCR assay. In this study, we demonstrated that FBTD was able to significantly enhance RFA-induced immune function in tumor-bearing mice by upregulating RFA-induced CD8+ killer T cells. Consistently, 10 mg/kg or 20 mg/kg FBTD therapy upregulated the percentage of IFNγ+ and TNFα+ CD8+ tumor infiltrating lymphocytes in tumor-bearing mice compared to the RFA alone or FBTD alone group. Mechanistically, we reported that FBTD inhibited the RFA-induced PD-1 and PD-L1 upregulation in vivo. In conclusion, we demonstrated that FBTD promoted the antitumor effects of RFA in lung tumor-bearing mice in this study.

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

To explore the antitumor effects of ethanol extract from Ventilago leiocarpa Benth (EEVLB) on sarcoma 180 (S180) tumor-bearing mice and the potential mechanism. 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. 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). 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.

Antitumor Effect of Zhihuang Fuzheng Soft Capsules on Tumor-Bearing Mice.

Chinese medicines (CMs) have been shown to have some advantages in preventing and controlling tumors. In this study, we investigated the antitumor effect of ZFSC by establishing a mouse model of HT-1080, A-549, and HCT-8 tumors. The result showed that tumor volumes of HT-1080 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group, and the high dose ZFSC showed the best antitumor effect. Tumor volumes of A-549 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group and showed a good dose-response relationship. There was no significant effect on human colon cancer, although inhibition trends disappeared in the bar chart. In order to verify the immunomodulatory effect of ZFSC, ELISA was used to analyze serums IL-2, TNF-α, and IFN in spleens. The results showed that ZFSC could enhance the immune function of tumor-bearing mice. ZFSC reduced IFN-γ and TNF-α content in the serum of HT-1080 tumor-bearing mice and inhibit PD1 and PDL1 and suggested that the antitumor mechanism of ZFSC on human fibrosarcoma could be attributed to inhibition of the PDL1/PD1 pathway.

Inhibition of Tumor Growth and Immunomodulatory Effects of Flavonoids and Scutebarbatines of Scutellaria barbata D. Don in Lewis-Bearing C57BL/6 Mice.

Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition of Scutellaria barbata D. Don (SB), an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effects in vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of 44.41 ± 5.44%, 33.56 ± 4.85%, and 27.57 ± 4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-β1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γ levels. Our results demonstrated that SB could inhibit tumor growth in vivo through regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer.

Preparation of selenium-enriched Bifidobacterium longum and its effect on tumor growth and immune function of tumor-bearing mice.

In this study, we demonstrated selenium (Se) accumulation in Bifidobacterium longum strain (B. longum) and evaluated the effect of Se-enriched B. longum (Se-B. longum) on tumor growth and immune function in tumor-bearing mice. Analysis using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) revealed that more than 99% of Se in Se-B. longum was organic, the main component of which was selenomethionine (SeMet). In the in vivo experiments, tumor-bearing mice (n=8) were orally administrated with different doses of Se-B. longum alone or combined with cyclophosphamide (CTX). The results showed that the middle and high dose of Se-B. longum significantly inhibited tumor growth. When Se-B. longum and CTX were combined, the antitumor effect was significantly enhanced and the survival time of tumor-bearing mice (n=12) was prolonged. Furthermore, compared with CTX alone, the combination of Se-B. longum and CTX stimulated the activity of natural killer (NK) cells and T lymphocytes, increasing the levels of interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α), and the leukocyte count of H22 tumor-bearing mice (n=12).

Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune modulation

BackgroundWe previously found that the low frequency magnetic fields (LF-MF) inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF may modulate immune function so as to inhibit tumor. We here investigated whether LF-MF can inhibit the proliferation and metastasis of melanoma and influence immune function.MethodsThe effect of MF on the proliferation, cell cycle and ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay, flow cytometry, and transmission electron microscopy. Lung metastasis mice were prepared by injection of 2 × 105 B16-F10 melanoma cells into the tail vein in C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days. Survival rate, tumor markers and the innate and adaptive immune parameters were measured.ResultsThe growth of B16-F10 cells was inhibited after exposure to the LF-MF. The inhibition was related to induction of cell cycle arrest and decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice model. Furthermore, the LF-MF modulated the immune response via regulation of immune cells and cytokine production. In addition, the number of Treg cells was decreased in mice with the LF-MF exposure, while the numbers of T cells as well as dendritic cells were significantly increased.ConclusionLF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma.

Ganoderma lucidum polysaccharides combined with low-dose cisplatin inhibits tumor growth and enhances the immune function of tumor-bearing mice

Objective To study the effects on inhibit tumor growth and enhance immune function of Ganoderma lucidum polysaccharide(GLP)combined with low-dose cisplatin in tumor-bearing mice.Methods 2 × 106 Lewis cells in 0.1 mL PBS were injected subcutaneously into the flanks of healthy female BALB/c nude mice (5～6 weeks old).When the tumor volume reached 100 mm3,mice were randomly assigned to 4 groups,control group (Oral gavage of 0.5 ml PBS and intraperitoneal injection of 0.5 ml),GLP group (gavage once every two days,40 mg/kg GLP in 0.5 ml),cisplatin group (intraperitoneal injection once every two days,2 mg/kg cisplatin in 0.5 ml) and the combination group (such as the above dose of cisplatin and GLP).After the treatment regimen was complete,the mice were sacrificed,and the tumors were removed,photographed,weighed,and prepared for histological analysis.The immune cells in spleen and peripheral blood were analyzed by flow cytometry.Results GLP can effectively increase anti-tumor effect of the small dose cisplatin,improve the survival of tumor-bearing mice,promote Th cells convert to Th1 in peripheral blood,increased the expression of CD 11c + on DC cell surface (GLP group 4.59％ VS the control group 1.06％,the combined group 7.21％ VS the cisplatin group 2.8％).Conclusion GLP can improve the immune function of tumor-bearing mice,had synergistic anti-tumor growth with low dose cisplatin,moreover,reduce renal toxic effects of cisplatin. Key words: Ganoderma lucidum polysaccharide (GLP); Cisplatin; Tumor-bearing mice; Immune function

Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice

To study the inhibitory effect of Danggui Buxue Tang (DBT), a compound traditional Chinese herbal medicine for supplementing blood, on tumor growth in tumor-bearing mice after inoculation of EL-4 cells, and its immune mechanism as well as its synergic effect in reducing toxicity of cytoxan (CTX). Experiment was carried out in tumor-bearing mice after inoculation of EL-4 cells. The mice were randomly divided into four groups after 7 days of the inoculation: untreated group, DBT-treated group [24 g/(kg x d)], CTX-treated group [7.5 mg/(kg x d)] and DBT plus CTX-treated group, with another ten normal mice as control. Inhibitory rate of tumor growth, survival time, immune function and variability of blood cells were measured in the mice during the experiment. After treatment of relevant interventions for 15 days, the tumor in the DBT-treated group, CTX-treated group and DBT plus CTX-treated group grew slower than the untreated group (P<0.05). Murine survival time in the DBT-treated group, CTX-treated group and DBT plus CTX-treated group was lengthened as compared with that in the untreated group (P<0.05). Compared with the untreated group, all kinds of immune indexes in the DBT-treated group and DBT plus CTX-treated group were significantly improved (P<0.05), while the immune indexes in the CTX-treated group were decreased (P<0.05). Compared with the CTX-treated group, all kinds of immune indexes in the DBT plus CTX-treated group were significantly improved (P<0.05). DBT can enhance the immune function in tumor-bearing mice and the inhibitory effect of DBT on tumor growth is related to the enhanced immune response. DBT can also increase the therapeutic effects and reduce the side effects of CTX.

Etudies of reducing poison and increasing effect of atractylodes macrocephala koidz on immune function of tumor-bearing mice after chemiotherapy

目的 研究白术对化疗后荷瘤小鼠免疫功能的影响.方法以S180荷瘤C57BL/6小鼠为模型,系统地研究白术对瘤重和脾细胞功能的影响.结果白术对荷瘤鼠化疗所引起的免疫功能低下具有明显的恢复作用,可显著提高化疗荷瘤鼠T细胞转化能力,明显促进化疗荷瘤鼠白细胞介素2(IL-2)分泌水平.结论白术能够拮抗肿瘤抗原和化疗所引起的免疫抑制。