Research progress on anti-tumor effects of lupeol / 中国药理学通报

Lupeol is a kind of triterpenoid widely found in a variety of Chinese herbal medicines and food-derived plants. It has multiple pharmacological activities such as antioxidant, anti-inflammatory and promoting skin healing. Recent studies have found that lupeol has anti-tumor effects on liver cancer, lung cancer, esophageal cancer and other tumor cells. The mechanisms of action are mainly by inhibiting tumor cell proliferation, inducing tumor cell apoptosis, and suppressing tumor cell invasion and metastasis. In this review, the anti-tumor research progress, pharmacological activities and molecular mechanisms of lupeol both in vitro and in vivo are reviewed and summarized to provide a theoretical basis for lupeol as a potential anti-tumor drug, and provide references for its anti-tumor mechanism.

Research progress on anti-tumor effects and mechanisms of triptolide and its combined application / 中国中药杂志

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.

Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect

Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl--glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DSPE-PEG) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the tumor penetration and the anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity.

Progress of anti-tumor mechanisms of statins / 肿瘤研究与临床

Statins are a kind of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, which are commonly used to reduce cholesterol level, and prevent cardiovascular and cerebrovascular diseases. In recent years, more and more researches have showed that statins could inhibit angiogenesis through inhibiting the proliferation, invasion and metastasis of cancer cells, and could promote cancer cells apoptosis and synergetically enhance the effect of radiotherapy and chemotherapy to play a potential anti-tumor role. This paper reviews the domestic and foreign research progresses of the anti-tumor mechanisms of statins.

Research on preparation process of andrographolide-glycyrrhizic acid polymeric micelles / 中国中药杂志

This study aimed to prepare andrographolide (AP)-loaded glycyrrhizic acid (GA) micelles (AP-GA)-PMs to enhance the solubility and anti-tumor effect of andrographolide. Firstly, andrographolide (AP) was used as the model drug and glycyrrhizic acid (GA) as carriers to prepare (AP-GA)-PMs. Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size, encapsulation efficiency (EE) and loading capacity of micelles. Finally, the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the (AP-GA)-PMs prepared by optimal process. The results showed that the prepared micelles under the optimal process had a nanosize of (127.11±1.38) nm, zeta potential of (-24.01±0.55) mV, the entrapment efficiency rate of (92.01±4.02)% , the drug loading rate of (51.44±1.24)% and high storage stability at 4 °C in 30 d, with slow but highly stable release. Moreover, (AP-GA)-PMs with the IC₅₀ value of 19.25 mg·L⁻¹ had a more synergistic and better anti-tumor effect in comparison with AP (IC₅₀=122.40 mg·L⁻¹) on HepG2 cells (P<0.01). In conclusion, the (AP-GA)-PMs prepared with glycyrrhizic acid as a carrier had a small particle size, large drug loading capacity, and high stability, and could significantly improve the anti-tumor effects of AP.

Research progress on anti-inflammatory and anti-tumor effects of sinomenine / 中国药理学通报

This review summarized some hot research fields in pharmacological effects of sinomenine such as anti-inflammatory, immunosuppressive, and anti-tumor effects. In addition to our exploration of its antinociceptive effect, we summarized above-mentioned pharmacological effects of sinomenine and its underly-ing mechanism, in order to provide an evidence for its clinical use.

Investigation of the Effective Dose of Agonistic 4-1BB Monoclonal Antibody in a Murine Colon Cancer Metastasis Model

PURPOSE: The aim of this study was to find the dose of agonistic 4-1BB monoclonal antibody (mAb) that results in optimal T cell activation. METHODS: Cancer was induced in mice by an intrahepatic parenchymal injection of 1x10(5) cells of CT26 cells. Cancer-carrying mice (n=84) were divided into seven groups and treated with either rat IgG or agonistic 4-1BB monoclonal antibody (mAb) (5microgram, 10microgram, 20microgram, 100microgram, 200microgram, or 300microgram). All treatments were administered intraperitoneally on days 7, 9, and 11. Mice from each group were sacrificed on days 14, 28, and 42. Harvested livers were weighed and the numbers of T cells in the splenocytes were analyzed with a FACS Vantage flow cytometer. RESULTS: Liver weights increased when 5microgram of agonistic 4-1BB mAb was administered, but showed no additional weight increase for doses greater than 10microgram. The absolute numbers of CD4+ and CD8+ T cells increased in groups treated with low doses of agonistic 4-1BB mAb (5microgram, 10microgram, or 20microgram), but did not increase in the groups treated with high doses of mAb (100microgram, 200microgram, or 300microgram). The levels of CD4/annexin V and CD8/annexin V increased as the dose increased, and the absolute cell numbers of CD4/annexin V were greater than those of CD8/annexin V. CONCLUSION: Liver weight, including the cancer mass, failed to increase at agonistic 4-1BB mAb doses greater than 10microgram. A high dose (> or =100microgram) of agonistic 4-1BB mAb resulted in lower counts of absolute T cells. This study suggests that a low dose (20microgram) of agonistic 4-1BB mAb can be used for optimal T cell activation in combination with other anti-cancer treatments.

Anti-tumor mechanisms of lymphopenic mice transferred with tumor-specific lymphocytes and immunized with mIL-21 tumor vaccine / 中华微生物学和免疫学杂志

Objective To explore the mechanism of anti-tumor effects of transferring tumor-specif-ic lymphocytes obtained from pre-immunized BALB/c mice with inactive rolL-21 tumor vaccine (mIL-21-Sp2/0)to syngeneic mice, associated with mIL-21 tumor vaccine immunization, in the condition of cyclo-phosphamide (Cy)-induced lymphopenia. Methods Activated lymphocytes of spleen and lymph nodes ob-tained from pre-immunlzed syngeneic mice with irradiated mIL-21-Sp2/0 cells were infused into BALB/cmice treated with Cy 2 days before, subsequently vaccinated with mlL-21 tumor vaccine, after 7 days, chal-lenged with Sp2/0 tumor cells, observed the growth of tumor of mice. T lymphocyte subsets differentiation was measured by flow cytometry (FCM) analysis. The proliferation and cytotoxie activities of activated lym-phocytes were analyzed by FCM, respectively, staining with CFSE and 7-AAD. The number of IFN-γ-secre-ting cells was evaluated by ELISPOT. Results The lymphopenic mice were transferred with activated lym-phocytes and inoculated with raiL-21 tumor vaccine might provide superior anti-tumor immunoprotection, re-tard tumor growth of the mice. The proliferating capabilities and killing rate of transferred tumor Ag-specific lymphocytes enhanced obviously, the number of IFN-γ-secreting cells was significantly higher compared with the control groups. Conclusion Under Cy-induced lymphopenia condition, tumor Ag-specific lymphocytes sensitized by raiL-21 tumor vaccine were transferred to mice and immunized with mlL-21 tumor vaccine at the same time, benefit the proliferation of transferred effective cells and immune cells itself, assist to form and sustain special anti-tumor effects.

Experimental study on anti-tumor effects of matrine on murine hepatocarcinoma cell H_(22) / 重庆医科大学学报

Objective:To study the anti-tumor effects of matrine on murine hepatocarcinoma cell line H 22 in vitro and in vivo .Methods:Cytotoxicity effect of matrine on cultured H 22 cells was determined by MTT assay in vitro .Apoptosis of cultured H 22 cells induced by matrine were determined with Annexiin V-FITC/PI affinity assay.Tumor-bearing BALB/C mice were used to observe the inhibitory effects of matrine on H 22 cells in vivo .The ultra micro-structured changes of H 22 cells were observed by transmission electron microscope in tumor-bearing BALB/C mice after treated with matrine.The expressions of Bcl-2 & Bax protein were detected by immunohistochemical technique and the staining densities of Bcl-2 & Bax protein were quantitated through computerized image processing.The data were analyzed with one-way ANOVA by means of SPSS 10.0.Results:Matrine could obviously inhibit the growth and induce the apoptosis of cultured H 22 cells.Matrine also had significant anti-tumor activity,on mice bearing H 22 hepatoma.The inhibitory rates were above 60.7% and 62.5% in higher and lower doses groups,respectively ( P

Influence of hydroxysafflor yellow A on the proliferation and expression of thrombospondin-l in human aortic endothelial cells / 重庆医科大学学报

0.065 7 g/L)causing inhibition of the proliferation of HAEC while a lower concentration(