Body Weight Of Tumor-bearing Mice Research Articles

PARP inhibitor Olaparib Enhances the Apoptotic Potentiality of Curcumin by Increasing the DNA Damage in Oral Cancer Cells through Inhibition of BER Cascade.

Although Olaparib (Ola, a PARP-inhibitor), in combination with other chemotherapeutic agents, was clinically approved to treat prostate cancer, but cytotoxicity, off-target effects of DNA damaging agents limit its applications in clinic. To improve the anti-cancer activity and to study the detailed mechanism of anti-cancer action, here we have used bioactive compound curcumin (Cur) in combination with Ola. Incubation of Ola in Cur pre-treated cells synergistically increased the death of oral cancer cells at much lower concentrations than individual optimum dose and inhibited the topoisomerase activity. Short exposure of Cur caused DNA damage in cells, but more increased DNA damage was noticed when Ola has incubated in Cur pre-treated cells. This combination did not alter the major components of homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways but significantly altered both short patch (SP) and long patch (LP) base excision repair (BER) components in cancer cells. Significant reduction in relative luciferase activity, expression of BER components and PARylation after Cur and Ola treatment confirmed this combination inhibit the BER activity in cells. Reduction of PARylation, decreased expression of BER components, decreased tumor volume and induction of apoptosis were also noticed in Cur + Ola treated Xenograft mice model. The combination treatment of Cur and Ola also helped in recovering the body weight of tumor-bearing mice. Thus, Cur + Ola combination increased the oral cancer cells death by not only causing the DNA damage but also blocking the induction of BER activity.

Long non-coding RNA HULC affects downstream-related targets to regulate migration and invasion of hepatoma cells

Objective: To investigate the effects of long non-coding RNA HULC on downstream related targets regulating the migration and invasion of hepatoma cells and theirs mechanism of action. Methods: The expression of highly upregulated in liver cancer (HULC) in hepatocellular carcinoma, and adjacent normal liver tissues and different hepatocellular carcinoma cells were detected by qPCR. The correlation between clinicopathological data of HULC and liver cancer patients were analyzed. Dual-luciferase reporter gene detected the interaction between HULC and miR-186. CCK-8 assay was used to detect the effect of HULC on proliferation of hepatocellular carcinoma cells. The change in hepatocellular carcinoma cell invasions ability after HULC inhibition was detected by transwell invasion assay and migration ability after inhibition of HULC was assessed by scratch assay. Differences between groups were compared using one-way ANOVA. P < 0.05 was considered statistically significant. Results: Compared with adjacent normal liver tissue, the expression of HULC in hepatocellular carcinoma was significantly higher [(1.79 ± 0.25) vs. (0.23 ± 0.05), P < 0.05]. The expression level of HULC was highest in hepatocellular carcinoma HepG3 cells. HULC specifically banded to the 3'UTR of miR-186 and regulated the expressional activity of miR-186. After inhibiting the expression of HULC, the proliferation of hepatocellular carcinoma cells was 72 h (0.35 ± 0.09) vs. (0.82 ± 0.16), P < 0.05; 96 h (0.42 ± 0.08) vs.(1.28 ± 0.19), P < 0.05), and the ability of migration and invasion was relatively decreased in 24 h (11.2% ± 1.6%) vs. (23.5% ± 3.6%), P < 0.05; 48 h (18.6% ± 3.0%) vs. (38.6% ± 5.6%), P < 0.05; 72 h (43.6% ± 5.3% ) vs. (69.6% ± 7.6%), P < 0.05]. After inhibiting the expression of HULC, the tumor volume and body weight of tumor-bearing mice were significantly reduced [volume (2.89 ± 0.29) cm(3) vs. (0.89 ± 0.18) cm(3), P < 0.05, body weight (3.18 ± 0.41) g vs. (0.45 ± 0.09) g, P < 0.05]. Conclusion: HULC plays an important role in the occurrence and development of hepatocellular carcinoma and can influence the biological behavior of hepatoma cells by regulating the expression of downstream-related targets.

Structural features of polysaccharides from edible jambo (Syzygium jambos) fruits and antitumor activity of extracted pectins

Jambo is a tropical fruit cultivated in Southeast Asia and tropical regions of America and Africa. After extraction, its polysaccharides were structurally characterized. Water soluble polysaccharides (WSP) were composed of GalA:Ara:Gal:Glc:Rha in 51:22:16:5:6 molar ratio, indicating the presence of pectic polysaccharides. Methylation analysis and NMR spectroscopy indicated the presence of homogalacturonan (HG), type II arabinogalactan and type I rhamnogalacturonan (RG-I). The HG/RG-I ratio was 88%, indicating greater amounts of smooth than hairy pectic regions. Hemicellulosic polysaccharides were extracted from the residue and fractionated by freeze-thaw procedure in two fractions (ASP-S and ASP-I). ASP-S was composed of Glc:Gal:Xyl:Ara:Man:Fuc:UA in a 45:16:20:3:8:5:2 molar ratio. Methylation analysis and 13C NMR spectroscopy indicated xyloglucan, xylan and mannan. Their relative proportion estimated on sugar linkage was 89%, 6% and 3%, respectively. ASP-I was composed mainly of xylose (99.5%) and its 13C NMR indicated a linear (1 → 4)-β-D-xylan. The biological activity of WSP was tested in Ehrlich tumor-bearing mice. After 21 days of oral treatment, the doses of 150 and 250 mg/kg WSP reduced expressively the tumor growth, similarly to the positive control methotrexate, and improved the body weight of tumor-bearing mice. Further studies are necessary to investigate the mechanisms of the WSP antitumor effect.

Hybrid polymeric micelles based on bioactive polypeptides as pH-responsive delivery systems against melanoma

The bioactive polymer poly(l-glutamic acid)n-b-poly(d, l-lactic acid)m was synthesized and used to form doxorubicin-loaded hybrid polymeric micelles to treat melanoma. These polymers exhibited pH-responsive changes in conformation, which controlled the diverse functionalities of the micelles. During circulation, poly(l-glutamic acid)n-b-poly(d, l-lactic acid)m protected Tat peptides on the micelles from proteolysis. Under tumor-acidic conditions, polymers with shorter poly(l-glutamic acid) blocks underwent a conformational change to form channels that accelerated the release of doxorubicin. The conformational change also exposed the Tat peptides to tumor cells, thereby promoting cellular internalization of the micelles. Enhanced cellular uptake of the micelles induced significant apoptosis of A375 melanoma cells in tumor-acidic conditions. In vivo studies demonstrated that the micelles with shorter poly(l-glutamic acid) blocks could effectively accumulate in tumor tissues, suppress tumor growth and help maintain the body weight of tumor-bearing mice. However, micelles with longer poly(l-glutamic acid) blocks did not undergo a conformational change under acidic conditions and performed poorly in both in vitro and in vivo evaluations. Our work provides a strategy for applying bioactive polymers to the rational construction of pH-responsive delivery systems for solid tumors and lends insight into possible conformational effects on the bioactivity of drug carriers.

Chronic alcohol consumption decreases the survival and compromises the antitumor immune response of mice bearing estrogen receptor positive E0771 breast cancer (TUM2P.898)

Abstract Epidemiological data convincingly indicate that chronic alcohol consumption increases the risk of breast cancer, especially estrogen receptor positive (ER+) breast cancer in women. The effect of alcohol on antitumor immunity and survival remains to be elucidated. Herein, we implanted ER+ E0771 breast cancer cells into the mammary pad of female C57BL/6 mice consuming 20% w/v alcohol for three months and examined the effect of chronic alcohol consumption on tumor growth, dynamic changes in the antitumor immune response and host survival. Alcohol did not affect primary tumor growth or the body weight of tumor-bearing mice; however, it decreased survival. Alcohol did not alter the percentage of MDSC, Treg, CD4+ T or CD8+ T cells in the spleen and blood, but increased theCD4/CD8 ratio. B cells decreased during tumor growth, and iNKT cells increased in the blood of alcohol-consuming mice. In non-tumor-bearing mice, alcohol increases IFN-γ-producing CD8+ T cells and NK cells. Four weeks after E0771 inoculation, the percentage of IFN-γ-producing CD8+ T cells and NK cells were lower in alcohol-consuming mice compared to water-drinking mice. Alcohol consumption also decreased survival of mice immunized with an E0771 cell lysate and boosted with αGalCer compared to water-drinking counterparts. Collectively, chronic alcohol consumption compromises antitumor immunity and decreases the survival of mice bearing ER+ breast cancer.

Inhibitory Effect of Vitamin C in Combination With Vitamin K3 on Tumor Growth and Metastasis of Lewis Lung Carcinoma Xenografted in C57BL/6 Mice

Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

In Vivo Phycocyanin Treatment of S180 Bearing-Mice: Increase in Immunic Function and Inhibition of Tumor Growth.

Objectives: To explore the effect of Phycocyanin (PC), with or without Cyclophosphamide(CY), on the growth inhibition of S180 cells and on the immunity improvement of S180-burdened mice. And to explore the anti-tumor mechanism of Phycocyanin.Methods: Each 0.2ml of S180 cells, a sarcoma cell line cells, at the concentration of 2×107 cells/ml, were inoculated into the right axilla of each test mouse. These mice were randomizely divided into 4 groups: PC-treated group (including 50−, 75− and 100mg/kg·d- subgroups); CY-treated group (20mg/kg·d); PC plus CY-treated group and normal saline(NS)-treated group which served as control group. 24 hours after the inoculation, PC or CY or PC plus CY or NS, at a final volume of 0.2ml, were injected to the abdominal cavity of each mouse in different group, and consecutively for 7 days. These mice were killed after the seventh treatment, then the peripheral blood, the whole tumor and the spleen were collected from each mouse. Each mouse's tumor weight was measured and blood routine exam was done. The serum level of IL-2, IFN-γ and TNF-α in each mouse was measured with ELISA method and the result was shown as pg/ml. Spleen cells from each mouse were collected and cultured respectively with ConA for 36 hours, and splenic T lymphocyte proliferation was measured.Results: PC inhibited the growth of S180 cells at all three tested dosages, 50mg/kg·d, 75mg/kg·d and 100mg/kg·d, and the inhibition rates were 41.41%, 37.37% and 36.36%, respectively. PC-treatment increased WBC counts in PB of tumor-bearing mice. The results also showed that PC-treatment and tumor-bearing situation increased the spleen weight and enhanced the splenic T lymphocyte proliferation induced by ConA. PC-treatment did not reduce the body weight of tumor-bearing mice. Among these three dosage, 50mg/kg·d was shown to have the best effect in the above mentioned parameters, as well as in the increase of IL-2, IFN-γ and TNF-α secretion. PC at dosages of 75mg/kg·d and 100mg/kg·d just increased the serum level of IFN-γ and TNF-α, without the increase of IL-2. Compared with PC-treatment, CY-treatment diminished serum level of IL-2, IFN-γ and TNF-α. PC (75mg/kg·d) combined with CY-treatment increased the tumor inhibition rate to 92.93%.Conclusions: 1, PC-treatment inhibited the growth of S180 cells. PC plus CY treatment showed more potential effect of growth inhibition. 2, PC enhanced markedly the immune function of S180-bearing mice in terms of increasing the spleen weight and the serum level of IFN-γ and TNF-α, and enhancing T lymphocyte proliferation induced by ConA. Those might account for the anti-tumor mechanism of PC. 3, PC-treatment antagonized the decrease in WBC count induced by CY-treatment. No obvious side effect of PC was found in the present study. Therefore, PC alone or combine with other chemotherapy drugs may offer a new approach in the treatment of hematological malignancies.

Effect of selenium on growth rate of canine mammary carcinoma cells in athymic nude mice

A canine mammary tumor cell line established from a carcinoma of the solid type was used in this study. In 2 separate experiments, athymic nude mice were inoculated subcutaneously with 5 × 10 6 viable tumor cells. All tumor-bearing mice received subcutaneous injections thrice weekly of 2 μg/g body wt of selenium as sodium selenite or phosphate buffered saline. Control, non-tumor-bearing mice were injected with either selenium or buffer. Selenium administration did not significantly alter the growth of non-tumor-bearing mice. However, body weight of tumor-bearing mice was reduced approximately 10%. The average volume of tumors in selenium treated mice was reduced 76% in experiment I and 74% in experiment II. (Supported in part by grant No. 81-7 from the American Cancer Society, Illinois Division, Inc., and USDA Grant No. 5901-9-0243.)