ABSTRACT
Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.
Subject(s)
Adult , Animals , Humans , Male , Mice , Middle Aged , Antibiotics, Antineoplastic , Pharmacology , Therapeutic Uses , Carcinoma , Drug Therapy , Cell Line, Tumor , Cell Proliferation , Framycetin , Pharmacology , Therapeutic Uses , Ki-67 Antigen , Genetics , Metabolism , Mice, Inbred BALB C , Mice, Nude , Pancreatic Neoplasms , Drug Therapy , Platelet Endothelial Cell Adhesion Molecule-1 , Genetics , Metabolism , Ribonuclease, Pancreatic , Genetics , MetabolismABSTRACT
Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.
ABSTRACT
This study investigated the molecular markers of DS-1-47, a component of an implantation- promoting traditional Chinese medicine consisting of Astragalus mongholicus, Atractylodes macrocephala, Scutellaria baicalensis and Dipsacales, in an attempt to clarify the molecular mechanism and action targets of DS-1-47. Controlled ovarian stimulation (COS) method was used to establish the implantation dysfunction models of mice. Animals were divided into normal pregnant group, COS model group and DS-1-47 group. Laser capture microdissection-double dimensional electrophoresis-mass spectrum (LCM-DE-MS) was used to analyze the uterine protein molecules that were possibly involved in the promotion of implantation. Twenty-three proteins in DS-1-47 group were significantly changed as compared to those in COS model group, with 7 proteins down-regulated and 16 proteins up-regulated. Except for some constituent proteins, the down-regulated proteins included collagen α-1 (VI) chain, keratin 7, keratin 14, myosin regulatory light chain 12B, myosin light polypeptide 9, heat shock protein β-7, and C-U-editing enzyme APOBEC-2; the up-regulated proteins included apolipoprotein A-I, calcium regulated protein-3, proliferating cell nuclear antigen, L-xylulose reductase, and calcium binding protein. These 23 proteins that were regulated by DS-1-47 represented a broad diversity of molecule functions. The down-regulated proteins were associated with stress and immune response, and those up-regulated proteins were related to proliferation. It was suggested that these proteins were important in regulating the uterine environment for the blastocyst implantation. By identification of DS-1-47 markers, proteomic analysis coupled with functional assays is demonstrated to be a promising approach to better understand the molecular mechanism of traditional Chinese medicine.
Subject(s)
Animals , Female , Mice , Pregnancy , Drugs, Chinese Herbal , Pharmacology , Embryo Implantation , Ovulation Induction , Proteome , Genetics , Metabolism , Uterus , Metabolism , PhysiologyABSTRACT
The study examined the effect of DS147, the bioactive component of the traditional herbal recipe Bangdeyun, on pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation (COS), and the underlying mechanisms. Female mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG) followed by an additional injection of 7.5 IU hCG 48 h later to establish embryo implantation dysfunction (EID) model. Pregnant mice were randomly divided into normal control group, COS group and DS147-treated groups. The pregnancy rate and the average implantation site were obtained on pregnancy day 8 (PD8). The side effect of 200 mg/kg of DS147 on naturally pregnant mice was also observed. Further, the uterine and ovarian tissue samples were collected on PD5 for measuring their weights, observing the development of the endometrium and ovary, and detecting the endometrial expression of MMP-2, TIMP-2, CD34 and angiogenin (ANG). The female mice treated with DS147 at doses of 100 to 800 mg/kg showed a higher pregnancy rate than those in COS group, and the highest pregnancy rate of 83.3% occurred in the 200 mg/kg DS147-treated group. Moreover, no obvious side effect was found in mice treated with 200 mg/kg DS147 on PD8 and PD16. The ovarian and uterine weights, and the expression levels of MMP-2, ANG and CD34 were significantly increased in DS147-treated groups when compared with COS group. The TIMP-2 expression level was much lower in DS147-treated mice than in COS mice and the ratio of MMP-2/TIMP-2 was much higher in DS147-treated group than in COS group, and even higher than normal control group. In all, these findings suggest that DS147 may improve pregnancy in mice with COS-induced EID by promoting matrix degradation and angiogenesis, and improving the development of corpus luteum and endometrial decidualization around the implantation window.
Subject(s)
Animals , Female , Mice , Pregnancy , Biological Factors , Pharmacology , Embryo Implantation , Ovulation Induction , Methods , Plants, MedicinalABSTRACT
The study examined the effect of DS147, the bioactive component of the traditional herbal recipe Bangdeyun, on pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation (COS), and the underlying mechanisms. Female mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG) followed by an additional injection of 7.5 IU hCG 48 h later to establish embryo implantation dysfunction (EID) model. Pregnant mice were randomly divided into normal control group, COS group and DS147-treated groups. The pregnancy rate and the average implantation site were obtained on pregnancy day 8 (PD8). The side effect of 200 mg/kg of DS147 on naturally pregnant mice was also observed. Further, the uterine and ovarian tissue samples were collected on PD5 for measuring their weights, observing the development of the endometrium and ovary, and detecting the endometrial expression of MMP-2, TIMP-2, CD34 and angiogenin (ANG). The female mice treated with DS147 at doses of 100 to 800 mg/kg showed a higher pregnancy rate than those in COS group, and the highest pregnancy rate of 83.3% occurred in the 200 mg/kg DS147-treated group. Moreover, no obvious side effect was found in mice treated with 200 mg/kg DS147 on PD8 and PD16. The ovarian and uterine weights, and the expression levels of MMP-2, ANG and CD34 were significantly increased in DS147-treated groups when compared with COS group. The TIMP-2 expression level was much lower in DS147-treated mice than in COS mice and the ratio of MMP-2/TIMP-2 was much higher in DS147-treated group than in COS group, and even higher than normal control group. In all, these findings suggest that DS147 may improve pregnancy in mice with COS-induced EID by promoting matrix degradation and angiogenesis, and improving the development of corpus luteum and endometrial decidualization around the implantation window.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the expression of angiopoietins in oral squamous cell carcinoma and relationship between the expression of angiopoietins and pathologic classification.</p><p><b>METHODS</b>The expression of Ang-1 and Ang-2 protein in samples from 42 oral squamous cell carcinoma and 16 oral normal mucosa were detected by immunohistochemical technique.</p><p><b>RESULTS</b>The expression of Ang-1 and Ang-2 was found in both oral squamous cell carcinoma and normal control. It was found Ang-1 expression alike in oral squamous cell carcinoma and control (P > 0.05). Ang-2 expressed at low level in control while strongly positive in oral squamous cell caroinoma and the level of Ang-2 expression in oral squamous cell caroinoma was related to pathologic classification (P < 0.05).</p><p><b>CONCLUSION</b>Ang-2 expression in oral squamous cell carcinoma is related to angiogenesis and pathological classification, which is probably involved in angiogenesis regulation, promotes the development and metastasis of oral squamous cell carcinoma.</p>
Subject(s)
Humans , Male , Middle Aged , Angiopoietin-1 , Angiopoietin-2 , Angiopoietins , Carcinoma, Squamous Cell , Mouth Mucosa , Mouth Neoplasms , Neoplasms , Neovascularization, PathologicABSTRACT
Objective To explore the role of intercellular adhesion molecule-1(ICAM-1)and lym- phocyte function-associated antigen-I(LFA-1)in the pathogenesis of Sjgren's syndrome(SS)and provide a theoretical basis for clinical therapy.Methods Immunohistochemical method was used to detect these two cellular adhesion molecules in labial salivary glands of primary Sjgren's syndrome patients and 15 healthy controls.Semiquantitative analysis was performed by image analysis software.Results①In salivary gland samples,the expression of both ICAM-1 and LFA-1 was significantly higher compared to that of controls(P