scholarly journals Enhancement of Recombinant Human Endostatin on the Radiosensitivity of Human Pulmonary Adenocarcinoma A549 Cells and Its Mechanism

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-dong Jiang ◽  
Yun Qiao ◽  
Peng Dai ◽  
Qin Chen ◽  
Jin Wu ◽  
...  

We observed the effects of endostar on the radiosensitivity of pulmonary adenocarcinoma A549 cells and found that endostar inhibited A549 cell growth under normoxia and hypoxia in time and dose-dependent manners; theD0andDqvalues in control and endostar groups were (1.36 and 1.30) versus (1.019 and 1.015) under normoxia and (1.693 and 1.39) versus (2.453 and 1.026) under hypoxia, respectively; SER was 1.04 under normoxia and 1.22 under hypoxia in endostar group; under normoxia, the apoptosis rates in control, radiotherapy, endostar and combination groups were15.9±0.57%,42.7±0.37%,19.9±0.48%, and41.5±0.38%, respectively, with no significant difference between combination and radiotherapy groups; there was significant difference in G2/M phase cells between combination and radiotherapy groups (P=0.028); under hypoxia, the apoptosis rates in the four groups were16.7±0.67%,30.1±0.95%,26.7±0.62%, and36.3±0.71%, respectively, with significant difference between combination and radiotherapy groups; G2/M phase cells were higher in combination group than radiotherapy group (P=0.000); G2/M phase cells were higher in hypoxic combination group than in normoxic combination group (P=0.003). Based on these results, we conclude that under hypoxia, endostar can enhance the radiosensitivity of A549 cells through G2/M arrest.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaofeng Shi ◽  
Ruiqin Du ◽  
Junmin Zhang ◽  
Yanping Lei ◽  
Hongyun Guo

Abstract Background Cedrus deodara (Roxb.) Loud (normally called as deodar), one out of four species in the genus Cedrus, exhibits widely biological activities. The Cedrus deodara total lignans from the pine needles (CTL) were extracted. The aim of the study was to investigate the anticancer potential of the CTL on A549 cell line. Methods We extracted the CTL by ethanol and assessed the cytotoxicity by CCK-8 method. Cell cycle and apoptosis were detected by a FACS Verse Calibur flow cytometry. Results The CTL were extracted by means of ethanol hot refluxing and the content of total lignans in CTL was about 55.77%. By the CCK-8 assays, CTL inhibited the growth of A549 cells in a dose-dependent fashion, with the IC50 values of 39.82 ± 1.74 μg/mL. CTL also inhibited the growth to a less extent in HeLa, HepG2, MKN28 and HT-29 cells. Conclusion At low doses, the CTL effectively inhibited the growth of A549 cells. By comparison of IC50 values, we found that A549 cells might be more sensitive to the treatment with CTL. In addition, CTL were also able to increase the population of A549 cells in G2/M phase and the percentage of apoptotic A549 cells. CTL may have therapeutic potential in lung adenocarcinoma cancer by regulating cell cycle and apoptosis.


2004 ◽  
Vol 22 (SI - Chem. Reactions in Foods V) ◽  
pp. S130-S132
Author(s):  
I. Nagamine ◽  
T. Yano ◽  
K. Endoh ◽  
T. Yamaki ◽  
T. Morimura ◽  
...  

Accumulating evidence suggests that overproduction of prostaglandin (PG) E2 attributable to induction of cyclooxygenase-2 plays an important role in the development of lung adenocarcinoma. Recently, we have reported that a PGE2 receptor, EP3 is involved in appearance of malignant phenotype of a lung adenocarcinoma cell (A549 cell). In line with our previous study, here we investigated if Src signaling could be involved in PGE2-stimulated growth of A549 cells via EP3. PGE2-dependent cell growth in A549 cell positively related to the activation of Src. A specific antagonist against EP3 abrogated the cell growth and Src activation in the cells stimulated with PGE2. Also, the inhibition of Src activity suppressed its downstream signaling related to cell growth as well as the cell growth in the cells treated with PGE2. These results indicate that PGE2-dependent activation of Src signaling via EP3 plays an important role in growth of A549 cells.


2020 ◽  
Vol 10 (8) ◽  
pp. 1218-1223
Author(s):  
Xinping Chen ◽  
Zhichao Ma ◽  
Juan Zhu ◽  
Weihua Xu ◽  
Junjie Hu ◽  
...  

The aim of this study was to investigate the effect of different concentrations of novel targeted nanodrugs based on miRNA on the antitumor activity and mechanism in cervical carcinoma A549 cells. The MTT method was used to determine the effect of different concentrations of novel targeted nanodrugs based on miRNA on A549 cell proliferation, and annexin V FITC/PI double staining flow cytometry was performed to analyze the effect of these nanodrugs on A549 cell apoptosis. Western blotting was performed to observe the effect of these nanodrugs on the expression of Bax, Bcl-2, and caspase-3-related genes involved in A549 cell apoptosis. Compared with the control group, the novel targeted nanodrugs based on miRNA significantly inhibited the proliferation of A549 cells in a time- and dose-dependent manner. Results of double staining flow cytometry demonstrated that these nanodrugs could increase the apoptotic rate of A549 cells in a dose-dependent manner 48 h later. Western blotting revealed that these nanodrugs could upregulate the expression of Bax and caspase3 genes and downregulate the expression of Bcl-2 gene. Nanodrugs display an obvious antitumor activity in vitro, and the underlying mechanism may be associated with the upregulation of Bax and caspase-3 gene expression and the downregulation of Bcl-2 gene expression.


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 ◽  
Author(s):  
Anil Shumroni ◽  
David Gupta

AbstractThe biodegradable and biodegradable natural polysaccharide has always been used as a drug delivery system, and has the following advantages: It can prolong the biological half life of the drug and reduce the side effects of the drug. This experiment aimed to prepare a 5-fluorouracil (5-FU) nanoparticle (P-5-FU) drug-loading system based on pectin, and explored a large number of pectin-based nano drug-loading systems. The galactose residue is a natural target that targets human hepatoma cell HepG2. MTT assay was used to determine the proliferation inhibition effect of drug-loaded pectin-based nanoparticles on HepG2 and A549 cells. MTT assay showed that P-5-FU inhibited the proliferation of HepG2 cells in a dose-dependent manner, and the effect was stronger than 5-FU. P-5-FU also inhibited the proliferation of A549 cells in a dose-dependent manner, but there was no significant difference compared with 5-FU. High performance liquid chromatography (HPLC) on two kinds of cells loaded with drug-loaded nanoparticles the uptake and targeting were measured. The results of cell uptake showed that the uptake of P-5-FU by HepG2 cells was significantly higher than that of 5-FU, but there was no significant difference in the uptake of P-5-FU and 5-FU by A549 cells. There was no significant difference in the uptake of P-5-FU and 5-FU between the two cells after the galactose-saturated ASGPR binding site. The results indicate that pectin-based nano drug-loaded particles can specifically target highly expressed cells.


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.


Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7057
Author(s):  
Mostafa I. Abdelglil ◽  
Sanaa O. Abdallah ◽  
Mohamed A. El-Desouky ◽  
Mohammad Y. Alfaifi ◽  
Serag Eldin I. Elbehairi ◽  
...  

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE.


2013 ◽  
Vol 641-642 ◽  
pp. 820-823
Author(s):  
Shu Jing Wang ◽  
Shan Jiang ◽  
Jia Liu ◽  
Fei Wang ◽  
Ning Chen ◽  
...  

7 peptide of Tumstatin(T-7 peptide) is composed of 185-191 amino acids. To study T-7 peptide antitumor activity to human non-small-cell carcinoma(A549), T-7 peptide was designed and synthesized by amino acid synthesizer. Its purity ran up to 98.45% by HPLC and MS. The effect of T-7 peptide on A549 cell growth was observed by MTT assay, growth curve and transmission electron microscopy(TEM). T-7 peptide had the effects of suppressing A549 cell growth and promoting its apoptosis, showing dose- and time-dependent. Its IC50 was 92.84 μg/ml. TEM also revealed that A549 cell treated with T-7 peptide appeared apoptotic morphology,such as cell pyknosis and mitochondrial vacuoles formed. While T-7 peptide had little effect on human umbilical vein endothelial cells(ECV304). These researches were significant to treat human non-small-cell carcinoma in the future.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
In-Seung Lee ◽  
InJoon Uh ◽  
Ki-Suk Kim ◽  
Kang-Hoon Kim ◽  
Jiyoung Park ◽  
...  

Objective. There is limited information of the anti-inflammatory effects of Rg3 on inflamed lung cells and tissues. Therefore, we confirmed the anti-inflammatory mechanism of ginsenoside Rg3 in inflamed human airway epithelial cells (A549) and tissues whether Rg3 regulates nuclear factor kappa B (NF-κB) activity.Methods. To induce the inflammation, IL-1β(10 ng/ml) was treated to A549 cells for 4 h. The effects of Rg3 on NF-κB activity and COX-2 expression were evaluated by western blotting analysis in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. Using multiplex cytokines assay, the secretion levels of NF-κB-mediated cytokines/chemokines were measured.Result. Rg3 showed the significant inhibition of NF-κB activity thereby reduced COX-2 expression was determined in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. In addition, among NF-κB-mediated cytokines, the secretion levels of IL-4, TNF-α, and eotaxin were significantly decreased by Rg3 in asthma tissues. Even though there was no significant difference, IL-6, IL-9, and IL-13 secretion showed a lower tendency compared to saline-treated human asthmatic airway epithelial tissues.Conclusion. The results from this study demonstrate the potential of Rg3 as an anti-inflammatory agent through regulating NF-κB activity and reducing the secretion of NF-κB-mediated cytokines/chemokines.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuan Xia ◽  
Xulong Zhang ◽  
Dejun Sun ◽  
Yumin Gao ◽  
Xiaoe Zhang ◽  
...  

Abstract Background This study aims to investigate the effects of water soluble particulate matter (WSPM) on the viability and protein expression profile of human lung adenocarcinoma cell A549 in the Bayou Obo rare earth mining area, and explore the influence of WSPM on the A549 cell cycle. Results It was found that WSPM can inhibit the viability of A549 cells and induce cell arrest in the G2/M phase. Compared with controls, exposure to WSPM10 and WSPM2.5 induced 134 and 116 proteins to be differentially expressed in A549 cells, respectively. In addition, 33 and 31 differentially expressed proteins were further confirmed, and was consistent with the proteomic analysis. The most prominent enrichment in ribosome-associated proteins were presented. When RPL6, RPL13, or RPL18A gene expression was inhibited, A549 cells were arrested in the G1 phase, affecting the expression of Cyclin D1, p21, RB1, Cyclin A2, Cyclin B1, CDC25A, CDK2, CHEK2 and E2F1. Furthermore, the La3+, Ce3+, Nd3+ and F- in WSPM also inhibited the viability of A549 cells. After 24 h of exposure to 2 mM of NaF, A549 cells were also arrested in the G2/M phase, while the other three compounds did not have this effect. These four compounds affected the cell cycle regulatory factors in A549 cells, mainly focusing on effecting the expression of CDK2, CDK4, RB1, ATM, TP53 and MDM2 genes. These results are consistent with the those from WSPM exposure. Conclusions These results revealed that WSPM from rare earth mines decreased the viability of A549 cells, and induced cell cycle G2/M phase arrest, and even apoptosis, which may be independent of the NF-κB/MYD88 pathway, and be perceived by the TLR4 receptor. The dysfunction of the cell cycle is correlated to the down-expression of ribosomal proteins (RPs). However, it is not the direct reason for the A549 cell arrest in the G2/M phase. La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. These results indicate the importance for further research into the relationship between APM and lung cancer.


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