scholarly journals Inhibitory effect of STAT3 gene combined with CDDP on growth of human Wilms tumour SK-NEP-1 cells

2016 ◽  
Vol 36 (3) ◽  
Author(s):  
Junrong Wang ◽  
Nina Zhang ◽  
Haijiang Qu ◽  
Guangxian You ◽  
Junhui Yuan ◽  
...  

To investigate the effects of signal transducer and activator of transcription 3 (STAT3) combined with cisplatin (CDDP) on the growth of human Wilms tumour (WT) SK-NEP-1 cell subcutaneous xenografts in nude mice and the possible mechanisms. Human WT SK-NEP-1 cells were subcutaneously transplanted to establish the BALB/c nude mice xenograft model. Mice were randomly divided into five groups: blank control group, adenovirus control group (NC group), STAT3 group, CDDP group and STAT3 plus CDDP group (combination group). Tumour volume and tumour weight were observed during the therapeutic process. The expression levels of STAT3, glucose regulatory protein 78 (GRP78) and BCL2-associated X protein (BAX) were evaluated by immunohistochemical analysis. Compared with the STAT3 group or CDDP group, the tumour weight and volume was significantly reduced in the combination group (P<0.05). No statistical significance was found in NC group compared with the blank control group (P > 0.05). Immunohistochemical analysis showed that STAT3, GRP78 and BAX protein levels in the combination group were significantly higher than those in STAT3 group and CDDP group (P<0.05). Exogenous STAT3 and CDDP may synergistically inhibit the xenograft tumour growth through up-regulation of BAX protein via GRP78.

2021 ◽  
Author(s):  
Jiang Yiyan ◽  
Wang Keke ◽  
Lou Zhefeng ◽  
Hong Dan ◽  
Min Tao

Abstract Background: Gastric cancer is one of the most common malignancy with high mortality rate in the world. Systemic chemotherapy is thought to be an important treatment. However, due to the unsatisfactory efficiency and obvious side effects, it is urgent to detect new therapy strategy for gastric cancer. This study was aimed to investigate the effects and mechanisms of ω-3 polyunsaturated acids (PUFAs) combined with 5-FU on the growth of gastric cancer cells in nude mice. Methods: BALB/C nude mice were injected subcutaneously with SGC7901 gastric cancer cells to establish a tumor-bearing mouse model. The tumor growth in vivo was observed. Morphological of tumor specimens was observed by HE staining. The mRNA levels of RhoA, RhoC and ROCK1 in tumor tissues were detected by qPCR, and their protein levels were detected by immunofluorescence and Western Blot. Meanwhile, apoptosis –related proteins were also determined by Western Blot.Results: Compared with the NC control group, the tumor volume and weight in ω-3 PUFAs and 5-Fu groups were insignificantly lower, but significantly lower in the combination group. Compared with the abundant blood supply in the NC group, HE staining showed multifocal tumor necrosis in the three intervention groups, and this change was the most prominent in the combination group. And qPCR results showed that the mRNA levels of RhoA in the combination groups were significantly lower than this in the other groups. Immunofluorescence showed that the level of RhoA protein in the three intervention groups decline in varying degrees, especially in the combination group. Western Blot showed that the protein level of RhoA in the three intervention groups were significantly lower than those in the NC control group, especially in the combination group. Meanwhile, the protein level of ROCK1 in both 5-FU group and the combination group were significantly lower, especially in the combination group. Compared with the control group, the levels of Bcl-2 and Caspase-9 decreased in the combination group, the level of cleaved Parp was increased at the same time.Conclusion: ω-3 PUFAs combined with 5-FU may inhibit tumor growth through the Rho/ROCK pathway and promote apoptosis by down-regulating the levels of Bcl-2 and Caspase-9 and induce the increase of cleaved Parp level.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Ji Qi ◽  
Ruiyue Ping ◽  
Shaoqun Zhang ◽  
Yanxiao Xu ◽  
Kai Wu ◽  
...  

Background. The safety of cervical rotatory manipulation (CRM) is still controversial, especially in patients with carotid artery atherosclerosis (CAS). The study aimed to investigate the effects of CRM on carotid plaques in vulnerability. Methods. 50 rabbits were randomly divided into four groups: model rabbits with CRM [CAS-CRM (n=15)]; model rabbits without CRM [CAS (n=15)]; normal rabbits with CRM [Normal-CRM (n=10)]; and Blank-control group (n=10). CAS disease models were induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. Then, CRM technique was performed in CAS-CRM and Normal-CRM groups for 3 weeks. In the end, determination of serum level of hs-CRP and Lp-PLA2, histological analysis under HE and Masson trichromic staining, and immunohistochemical analysis with CD34 and CD68 antibody were completed in order. Results. Carotid stenosis rates on successful model rabbits ranged from 70% to 98%. The CAS-CRM group had an increased level of hs-CRP (P<0.05), in comparison with the CAS group, whereas effects were not significant between the Normal-CRM group and Blank-control group. In comparison with the CAS group, the positive expression of CD34 and CD68 in the CAS-CRM group increased significantly (P<0.05). Conclusion. CRM therapy may increase the vulnerability of carotid plaque in rabbits with severe CAS.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 288-288
Author(s):  
Eugene K. Lee ◽  
Jinesh Gerald ◽  
Ashish M. Kamat

288 Background: Intravesical BCG is the gold standard for non-muscle-invasive bladder cancer (NMIBC). However, many patients do not respond to therapy while others relapse and/or progress. As a result, there remains a need for therapies that can enhance the efficacy of BCG. We explore the efficacy of lenalidomide, an immunomodulatory agent used in multiple myeloma and myelodysplastic syndrome, in combination with BCG in vitro and in an in vivo bladder cancer model. Methods: We studied the effects of lenalidomide in combination with BCG induced cytokines in MBT-2 cells using PI-FACS. For in vitro studies, we used 10 and 100 nM of lenalidomide in combination with TNF-a and FasL. We then performed Western blotting for cell cycle and apoptosis regulatory proteins. Subsequently, we tested the efficacy of this combination in an immunocompetent murine model of bladder cancer with MBT-2 cells in C3H mice using the flank injection method. Drug dosages were 30 mg/kg for lenalidomide and 105 CFU of BCG. Tumor growth curves were created for the control, lenalidomide, BCG and combination treatment mice groups. Immunohistochemistry (IHC) was then performed using antibodies against proteins related to cell cycle, apoptosis, angiogenesis and immune response. Results: PI-FACS identified increased DNA fragmentation in the combinations of lenalidomide and TNF-a and FasL compared to control and each agent alone. Using Western blotting, we demonstrated that the combination resulted in apoptosis via caspase-3 activation. In the murine model, combination therapy resulted in a statistically significant decreased tumor size compared to the control group. While the BCG alone and lenalidomide alone groups did show a trend toward smaller tumor, they did not reach statistical significance. Furthermore, the TUNEL assay showed a substantial increase in apoptosis only in the combination group. Immunohistochemistry demonstrated decreased angiogenesis in all treatment groups compared to control, as well as, decreased T-cell infiltration. Conclusions: Our study demonstrates a potential role for the immunomodulatory agent, lenalidomide, in combination with BCG for NMIBC. This in vivo model serves as a template for future clinical trials.


2013 ◽  
Vol 781-784 ◽  
pp. 587-590
Author(s):  
Bin Liu ◽  
Jie Yun Sun ◽  
Li Yu

In this study we investigated the effect of plant polyphenol PTK inhibitor genistein on subcutaneous human transplant ovarian cancer tumor of nude mice. All 30 cases of nude mice are used to establish subcutaneous xenograft models of human ovarian cancer, and divided into 4 groups: Control group (containing 0.04% DMSO of saline); Genistein group (containing 0.2 mg / kg and 0.4 mg/kg two concentrations, subcutaneous injection); Cisplatin group (4 mg/kg, i.v.); Genistein and Cisplatin combination group. The transplanted tumor growth and weight changes of nude mice in different groups on 7, 14, 21 and 28 days were observed and histopathological examined. The results showed that the growth of SKOV3 xenograft tumor was significantly inhibited in 0.4 mg/kg Genistein group. Compared with control group, the tumor weights were decreased, the tumor volumes were reduced, and there was a significant increase in the area of necrosis, but no significant effects were showed on the weights of nude mice. 0.4 mg/kg Genistein (s.c.) in combination with 4 mg/kg Cisplatin (i.v.) enhanced the inhibitory effect. The results provide evidence for the potential usefulness of Genistein in the prevention and treatment of human ovarian carcinoma.


2020 ◽  
Author(s):  
Qitian Chen ◽  
Ran Chen ◽  
Youhong Dong

Abstract Background: Inhibitory effect of endostar combined with radiotherapy on gastric cancer (GC) animal models and its effect on transforming growth factor-β1 (TGF-β1) and inter- leukin-10 (IL-10) were evaluated. Methods: Forty mice of a GC model xenograft tumors were prepared and randomly divided into blank control group, endostar group, radiotherapy group and endostar combined with radiotherapy group (combination group). From the 14th day, a vernier caliper was used for measuring the long and short diameters of the xenograft tumors. The formula V = ab2/2 was used for calculating the tumor volume and to obtain its average value. Tumor growth curves were plotted to calculate the tumor inhibition rate. The growth of xenograft tumors and the behavioral changes of mice were observed. Enzyme-linked immunosorbent assay (ELISA) was used for detecting the expression levels of IL-10 and TGF-β1. Results: The tumor growth in the combination group was significantly inhibited and the tumor volume was the smallest compared with the other groups (p<0.05). Compared to the blank control group, the tumor inhibition rate was 11.8% in endostar group, 33.0% in radiotherapy group and 52.1% in combination group (p<0.01). Endostar combined with radiotherapy had an interaction in decreasing the expression levels of TGF-β1 and IL‑10 (F=4.35 and 5.12, p<0.05). Leucocyte count was significantly higher in control and combination groups than that in endostar and radiotherapy groups. The body weight of mice in endostar and radiotherapy groups decreased after treatment (p<0.05). The body weight of mice after treatment in control and combination groups increased, with a statistically significant difference compared to that before treatment (p<0.05). There was a statistically significant difference among all groups after treatment (F=198.1, p<0.01). Conclusions: Endostar combined with radiotherapy can inhibit tumor growth and downregulate the expression levels of TGF-β1 and IL-10 through synergistic action.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 209-209
Author(s):  
Xiaofei Chen ◽  
Yunfen Zhu ◽  
Yongkang Yang ◽  
Jiqian Xiang ◽  
Hongqing Yin ◽  
...  

Abstract Objective: In this study, we estimate the effects of probiotics, Chinese herbal medicine and antibiotics on chicken protein, fat, ash, some kind of amino acids and fatty acids, tenderness and other physical and chemical properties. Method: 240 hens were divided into six groups, including blank control group, probiotic group, antibiotic group, Chinese herbal medicine group (Three parallel groups were set in the Chinese herbal medicine group: 0.3%, 0.6% and 1%). Hens were fed on restricted diets for more than 120 days. Collecting six breast samples from each group randomly and assaying those items described in the objective. In this study, we performed some determination methods, such as HPLC, GC, Kjeldahl and Soxhelt Method. Data were collected by Excel and analyzed by SPSS18.0 software. The results were expressed as the mean ± SD. One-way ANOVA followed by Duncan’s test was performed to determine statistical significance. ResultThe results showed that the contents of protein, fat, amino acid and fatty acid in chicken were not different significantly among these groups (P &gt; 0.05). So did the value of shear (P &gt; 0.05). Inosine acid content in 0.6% & 1% Chinese herbal medicine group was increased significantly (P &lt; 0.05). The ash value was decreased significantly in 1% Chinese herbal medicine group (P &lt; 0.05). Significance and Innovation: There are many alternatives of antibiotics in livestock and poultry breeding based on Chinese herbal medicine in China. Our study helps to illustrate the positive effect of Chinese herbal medicine on animal feeding and lay a foundation for the future rational application of Chinese herbal medicine in non-antibiotic feeding. Meanwhile, similar reports have not been found internationally. Conclusion Adding proper amount of Chinese herbal medicine in diet can promote the production of inosine acid and enhance the taste of meat, reduce the ash content similarly.


2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Xin Wen ◽  
Xin-Rui Han ◽  
Shao-Hua Fan ◽  
Zi-Feng Zhang ◽  
Lu Chen ◽  
...  

The study investigated the effects of X-chromosome-linked inhibitor of apoptosis (XIAP) gene silencing on the radiosensitivity of esophageal cancer (EC) cells. Western blotting was used to select EC cell lines with XIAP overexpression. Selected EC9706 and KYSE30 cell lines were both divided into four groups: the blank control group, the negative control (NC) group (transfected with pBSHH1), the siRNA-enhanced group (transfected with pBSHH1-XIAP1-siRNA), and the siRNA-decreased group (transfected with pBSHH1-XIAP2-siRNA). Expressions of XIAP were measured by reverse-transcription quantitative PCR (RT-qPCR) and Western blotting, cell survival and viability by MTT assay and colony formation assay, and cell apoptosis by flow cytometry, respectively. Caspase-3 and caspase-9 activity were detected using caspase-3 and caspase-9 activity detection kits. A nude mice model of EC9706 cell line was established to measure tumorigenesis ability. Compared with the NC group, XIAP mRNA and protein expressions were decreased, caspase-3 and caspase-9 activity and apoptosis were up-regulated, and cell survival rate and colony-forming efficiency were lower in the siRNA-enhanced and siRNA-decreased groups in both the cell lines; while the opposite trends were found in the siRNA-decreased group compared with the siRNA-enhanced group. Tumor weight and volume of nude mice were decreased in the siRNA-enhanced and siRNA-decreased groups than those in the NC group, and were elevated in the siRNA-decreased group compared with the siRNA-enhanced group. These results indicate that XIAP gene silencing would strengthen the radiosensitivity of EC9706 cells, which provides a novel target for the treatment of EC.


2020 ◽  
Author(s):  
Chen Qitian ◽  
Chen Ran ◽  
Dong Youhong

Abstract Background: Inhibitory effect of endostar combined with radiotherapy on gastric cancer (GC) animal models and its effect on transforming growth factor-β (TGF-β)1 and inter- leukin-10 (IL-10) were evaluated.Methods: Forty mouse models of GC xenograft tumors were prepared and randomly divided into blank control group, endostar group, radiotherapy group and endostar combined with radiotherapy group (combina- tion group). From the 14th day, a vernier caliper was used for measuring the long and short diameters of the xenograft tumors. The formula V = ab2/2 was used for calculating the tumor volume and to obtain its average value. Tumor growth curves were plotted to calculate the tumor inhibition rate. The growth of xenograft tumors and the behavioral changes of mice were observed. ELISA was used for detecting the expression levels of IL-10 and TGF-β1.Results: The tumor growth in the combination group was significantly inhibited, and the tumor volume was finally the smallest compared with the other groups (p<0.05). Compared to the blank control group, the tumor inhibition rate was 11.8% in endostar group, 33.0% in radiotherapy group and 52.1% in combination group (p<0.01). Endostar combined with radiotherapy had an interaction in decreasing the expression levels of TGF-β1 and IL‑10 (F=4.35 and 5.12, p<0.05). Leucocyte count was significantly higher in control and combination groups than that in endostar and radiotherapy groups. The body weight of mice in endostar and radiotherapy groups decreased after treatment (p<0.05). The body weight of mice after treatment in control and combination groups increased, with a statistically significant difference compared to that before treatment (p<0.05). There was a statistically significant difference among all groups after treatment (F=198.1, p<0.01).Conclusions: Endostar combined with radiotherapy can inhibit tumor growth and downregulate the expression levels of TGF-β1 and IL-10 through synergistic action.


2021 ◽  
Vol 13 (8) ◽  
pp. 1430-1436
Author(s):  
Jianghong Zhou ◽  
Shuo Zhang ◽  
Yin Tao ◽  
Jinjin Wang ◽  
Huan Chen ◽  
...  

Nano-albumin-mediated different doses of glutaraldehyde (GLA) were used in cervical cancer nude mice to observe the expression of p53, Bax protein and genes in transplanted tumors and explore the mechanism of GLA on cervical cancer. Cervical cancer Hela cells were cultured. 20 nude BALB/C-nu female mice were selected to establish transplanted tumor models and separated into control group (n = 5) and GLA group (n = 15). Grouping of glutaraldehyde (GLA)-loaded human serum albumin nano-carriers (GLA-HSANC) drugs was done and separated into GLA low-dose (0.06 µmol/mg) and medium-dose (0.12 µmol/mg) and high-dose group (0.18 µmol/mg) followed by assessing xenograft tumor apoptosis, p53 and Bax expression and Hela cell cycle. The shape and structure of various organs of nude mice were normal. The volume of transplanted tumors, tumor markers CA125 and CEA in different dose groups were lower than the control group. The tumor inhibition rate, growth inhibition rate of transplanted tumors, the number of apoptotic cells in transplanted tumors, p53, Bax protein and mRNA expression were all opposite in a dose dependent manner. Compared with the control group, the number of cells in G1 phase of other groups was higher with lower cell number in S phase dose-dependently. GLA nano-albumin particles-mediated p53 targeting cervical cancer tumors can significantly promote tumor cell apoptosis possibly via upregulating p53 and Bax, and increasing cells in G1 phase.


2020 ◽  
Author(s):  
Shanshan Wang ◽  
Liu Yangyang ◽  
Xu Xiaohao ◽  
Liu Tiejun ◽  
Shu Zunhua ◽  
...  

Abstract BackgroundHepatoma is one of the most common malignant tumors in my country, and its occurrence and development play an important role in the molecular mechanism of hypoxia microenvironment and angiogenesis. Huazhengsanji prescription(HZSJ) is an empirical prescription for the treatment of liver cancer, but its specific anti-tumor molecular mechanism is still unclear, and whether it has a synergistic effect with cisplatin(DDP), a chemotherapy drug for liver cancer, has not been reported yet. This article discusses the inhibition of the proliferation and migration of HepG2 hepatocarcinoma cells and the difference in the expression of HIF-1α and VEGF when the HZSJ, DDP and the two are used in combination, and compares and analyzes the mechanism of the HZSJ in enhancing the anticancer sensitivity of chemotherapeutics.MethodsHepG2 Hepatoma cells were divided into blank control group, hypoxia model group, DDP group, HZSJ group, HZSJ+DDP group, and the hypoxia environment was induced by the CoCl2 method. MTT method detects cell proliferation ability, scratch test detects cell migration ability, immunofluorescence method and western blot detect HIF-1α and VEGF protein expression.ResultsHZSJ has the effect of inhibiting the proliferation and migration of HepG2 cells, and has obvious concentration-dependent; The combined application of HZSJ and DDP has significantly stronger inhibitory effect on cell proliferation than the HZSJ group (P<0.01) and the DDP group (P<0.01, P<0.001). High-dose HZSJ can inhibit the migration ability of HepG2 cells (P<0.01); the combination of HZSJ and DDP can significantly reduce the migration rate of HepG2 cells after induction (P<0.01, P<0.01, P <0.01). The results of immunofluorescence and western blot showed that: compared with the blank control group, the expression levels of HIF-1α and VEGF protein in the model group were significantly increased (P<0.05, P<0.01, P<0.001); compared with the model group and DDP The expression of HIF-1α protein in the high-dose HZSJ group (200μg/mL) and the combination group decreased (P<0.05, P<0.01, P<0.001), but there was no difference between the groups. Compared with the model group, the high-dose HZSJ group (200μg/mL) can reduce the expression of VEGF (P<0.05); compared with the model group and the DDP group, the combination group can reduce the expression of VEGF (P< 0.01, P<0.001), and has obvious concentration dependence.ConclusionsHZSJ can inhibit the proliferation and migration of HepG2 hepatoma cells under hypoxia, which may be related to the reduction of HIF-1α and VEGF expression, and its increase in the anticancer sensitivity of the chemotherapy drug DDP may be related to both The synergistic inhibition of VEGF expression is related.


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