scholarly journals Astragalus Polysaccharides Alleviate Lung Adenocarcinoma Bone Metastases by Inhibiting the CaSR/PTHrP Signaling Pathway

2021 ◽  
Author(s):  
Xiaoting Ma ◽  
Cong Wang ◽  
Jing Yu
Keyword(s):  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
A549 Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
And Migration ◽  
Related Proteins ◽  
Proliferation And Invasion ◽  
Proliferation And Migration

Abstract Background: To expore the possible effect and mechanism of Astragalus Polysaccharide (APS) on bone metastasis of lung adenocarcinoma.Methods: The culture media of osteoclast (OC) precursor cells, osteoblasts (OBs) and A549 cells were constructed respectively. TRAP staining was used to detect the effect of APS on OC differentiation. Alizarin red staining was used to detect the effect of APS on OB differentiation. The expressions of OC differentiation related proteins and OB specific proteins were detected by Western blotting. The effects of APS on the proliferation and migration of A549 cells were detected by CCK-8 and Transwell assay, respectively. The effect of APS on A549 induced apoptosis was analyzed by flow cytometry. The expression of calcium sensing receptor (CaSR) / parathyroid hormone-related protein (PTHrP) signal pathway related proteins was detected by Western blotting. The mouse model of bone metastasis of lung adenocarcinoma was established. The occurrence of bone metastasis of lung adenocarcinoma in mice was verified by micro CT. The inhibition of APS on bone metastasis and the promotion of tumor cell apoptosis were detected by HE staining and TUNEL assay.Results: APS inhibited the formation of receptor activator of nuclear factor-κB ligand (RANKL) induced OCs and promoted the differentiation of OBs in a concentration dependent manner. APS inhibited RANKL induced OC differentiation and the expression of related proteins, and promoted OB differentiation and the expression of related proteins. APS inhibited the proliferation and migration of A549 cells and promoted apoptosis in a concentration dependent manner. APS may inhibit the proliferation and invasion of A549 cells by inhibiting CaSR / PTHrP signaling pathway, and inhibit the expression of CaSR / PTHrP signaling pathway related proteins. In vivo experiments confirmed that APS inhibited bone metastasis of lung adenocarcinoma.Conclusions: APS can inhibit the proliferation and invasion of lung adenocarcinoma cells by inhibiting the CaSR / PTHrP pathway, and then affect the balance of OCs and OBs in the bone microenvironment, so as to protect the bone metastasis of lung adenocarcinoma.

scholarly journals Protective Effect of Silymarin against Rapamycin-induced Apoptosis and Proliferation Inhibition in Endothelial Progenitor Cells

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Peng Zhang ◽  
Guohua Han ◽  
Pei Gao ◽  
Kun Qiao ◽  
Yusheng Ren ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Concentration Dependent Manner ◽  
Inhibition Of Proliferation ◽  
And Migration ◽  
Proliferation And Migration

For this study, peripheral blood samples were collected from human volunteers. Mononuclear cells (MNC) were separated by density centrifugation and were induced to differentiate into endothelial progenitor cells (EPCs) in vitro. Different concentrations of rapamycin and silymarin were introduced to the EPCs over 24 hours and then EPCs were analyzed for proliferation, migration, apoptosis and angiogenesis. Compared with the control group, rapamycin (1, 10, 100 ng/mL) inhibited the proliferation and migration of EPCs in a concentration dependent manner ( P<0.05). Silymarin (50, 100 μg/mL) enhanced the proliferation and migration of EPCs and inhibited apoptosis in a concentration dependent manner ( P<0.05). By adding rapamycin (1 ng/mL) and silymarin (25, 50, 100 μg/mL) over 24 hours, silymarin inhibited the pro-apoptotic effect of rapamycin on EPCs, and reversed the inhibition of proliferation, migration and angiogenesis of EPCs by rapamycin ( P<0.05).

scholarly journals STIP1 Regulates Proliferation and Migration of Lung Adenocarcinoma Through JAK2/STAT3 Signaling Pathway

2019 ◽  
Vol Volume 11 ◽  
pp. 10061-10072 ◽  
Author(s):  
Xiangjun Guo ◽  
Zhongyi Yan ◽  
Gongming Zhang ◽  
Xiang Wang ◽  
Yun Pan ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Alkaloid Extract of Moringa oleifera Lam. Exerts Antitumor Activity in Human Non-Small-Cell Lung Cancer via Modulation of the JAK2/STAT3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jing Xie ◽  
Lin-jie Peng ◽  
Ming-rong Yang ◽  
Wei-wei Jiang ◽  
Jia-ying Mao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Moringa Oleifera ◽  
A549 Cells ◽  
Cycle Arrest ◽  
And Migration ◽  
Related Proteins ◽  
Moringa Oleifera Lam ◽  
Proliferation And Migration

Lung cancer is one of the most common malignant tumors diagnosed worldwide. Moringa oleifera Lam. is a valuable medicinal plant native to India and Pakistan. However, the antilung cancer activity of M. oleifera alkaloid extract (MOAE) is unknown. The present study aimed to evaluate the regulatory effect of MOAE on A549 cells by examination of the proliferation, apoptosis, cell cycle, and migration of cells and to elucidate the possible mechanism of action of MOAE. We tested five types of cancer cells and four types of lung cancer cells and found MOAE exerted the strongest growth inhibitory effect against A549 cells but had low toxicity to GES-1 cells (human gastric mucosal epithelial cells). Simultaneously, MOAE induced apoptosis and increased the expression of the apoptosis-related proteins caspase-3 and caspase-9 in A549 cells. Furthermore, MOAE induced cell cycle arrest in the S phase through a decrease in the expression of the proteins cyclin D1 and cyclin E and an increase in the expression of the protein p21. MOAE also inhibited the migratory ability of A549 cells and decreased the expression of the migration-related proteins, matrix metalloproteinase (MMP) 2 and MMP9. In addition, the phosphorylation level of JAK2 and STAT3 proteins was decreased in MOAE-treated A549 cells. Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.

scholarly journals TEEG Induced A549 Cell Autophagy by Regulating the PI3K/AKT/mTOR Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Lu Shi ◽  
Yijun Tu ◽  
Yu Xia ◽  
Siqi Ye ◽  
Chaozhi Ma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
A549 Cell ◽  
A549 Cells ◽  
Mtor Signaling ◽  
Immunofluorescence Staining ◽  
Nsclc Cell Line ◽  
Dependent Manner ◽  
Mtor Signaling Pathway ◽  
Concentration Dependent Manner

TEEG (3β,16β,23-trihydroxy-13,28-epoxyurs-11-ene-3-O-β-D-glucopyranoside) is derived from the chloroform extract of the Chinese medicine formula Shenqi San (CE-SS). In the present study, we aimed to elucidate the anticancer effect and possible molecular mechanism underlying the action of TEEG against the human non-small cell lung cancer (NSCLC) cell line A549 in vitro. A549 cells were incubated with different concentrations of TEEG. Cell proliferation was assessed by MTT assay. Autophagy was evaluated by immunofluorescence staining. Autophagy-associated proteins were examined by Western blot analysis. TEEG markedly inhibited A549 cell proliferation in a concentration-dependent manner. Immunofluorescence staining showed that TEEG induced autophagy in A549 cells. The LC3-II : LC3-I conversion ratio and the expression of Beclin-1, Atg5, Atg7, and Atg12 increased with the concentration of TEEG. In addition, increased TEEG concentration enhanced the expression of Class III p-PI3K and reduced the expression of Class I p-PI3K, p-AKT, p-mTOR, and p-P70S6K. These results indicate that TEEG induces autophagy of A549 cells through regulation of the PI3K/AKT/mTOR signaling pathway.

scholarly journals The release of tryptase from mast cells promote tumor cell metastasis via exosomes

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hui Xiao ◽  
Mudan He ◽  
Guogang Xie ◽  
Yanan Liu ◽  
Yuxia Zhao ◽  
...  
Keyword(s):  
Mast Cells ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Umbilical Vein ◽  
A549 Cells ◽  
Stat Signaling ◽  
Promote Tumor Cell ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells ◽  
Proliferation And Migration

Abstract Background Cancer cells release exosomes and can be taken up by mast cells (MCs), but the potential functional effects of MCs on tumor metastasis remain unknown. Method Exosomes were isolated from the lung adenocarcinoma cell line A549, and the uptake of PKH26-labeled exosomes by bone marrow MCs was examined via flow cytometry and fluorescence microscopy. Cytokines and tryptase in MC supernatant were analyzed using an ELISA kit, and the presence of tryptase was evaluated by Western blotting. Cell proliferation and migration were determined through CCK-8 and transwell assays. Proteins in the tryptase-JAK-STAT signaling pathway were detected by Western blotting. Results In this study, we show that exosomes from A549 cells can be taken up by MCs. Moreover, A549 exosomes contain stem cell factor (SCF) to MCs and subsequently induce the activation of MCs through SCF-KIT signal transduction, which leads to MC degranulation and the release of tryptase. Tryptase accelerates the proliferation and migration of human umbilical vein endothelial cells (HUVECs) through the JAK-STAT signaling pathway. Conclusions Our results reveal a mechanism for metastasis in which exosomes can transfer SCF to and activate MCs, which can affect the release of tryptase and the angiogenesis of HUVECs.

scholarly journals TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment

2021 ◽  
Vol 22 (20) ◽  
pp. 10930
Author(s):  
Shuai Guo ◽  
Xue Bai ◽  
Sai Shi ◽  
Yawen Deng ◽  
Xianjiang Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Normal Lung ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
In Vivo Experiments ◽  
Incidence And Mortality ◽  
And Migration ◽  
Proliferation And Migration

Lung cancer has the highest rate of incidence and mortality among all cancers. Most chemotherapeutic drugs used to treat lung cancer cause serious side effects and are susceptible to drug resistance. Therefore, exploring novel therapeutic targets for lung cancer is important. In this study, we evaluated the potential of TMEM16A as a drug target for lung cancer. Homoharringtonine (HHT) was identified as a novel natural product inhibitor of TMEM16A. Patch-clamp experiments showed that HHT inhibited TMEM16A activity in a concentration-dependent manner. HHT significantly inhibited the proliferation and migration of lung cancer cells with high TMEM16A expression but did not affect the growth of normal lung cells in the absence of TMEM16A expression. In vivo experiments showed that HHT inhibited the growth of lung tumors in mice and did not reduce their body weight. Finally, the molecular mechanism through which HHT inhibits lung cancer was explored by western blotting. The findings showed that HHT has the potential to regulate TMEM16A activity both in vitro and in vivo and could be a new lead compound for the development of anti-lung-cancer drugs.

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