scholarly journals Matrine induces apoptosis via targeting CCR7 and enhances the effect of anticancer drugs in non-small cell lung cancer in vitro

2018 ◽  
Vol 24 (7) ◽  
pp. 394-399 ◽  
Author(s):  
Jiangtao Pu ◽  
Xiaojun Tang ◽  
Xiang Zhuang ◽  
Zhi Hu ◽  
Kaiming He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Anticancer Drugs ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
Gene Expressions

This study mainly investigated the effects of matrine on cell apoptosis and the effects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines (A549 and LK2 cells). The results showed that matrine (≥10 μM) caused a significant inhibition on cell viability and 10 and 100 μM matrine induced cell apoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells. In addition, matrine significantly down-regulated C-C chemokine receptor type 7 (CCR7) expression, and blocking the down-regulation of CCR7 by exogenous chemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects of apoptosis genes in A549 cells. The results were further validated in LK2 cells that matrine regulated apoptosis gene expressions, which were reversed by CCL21 treatment. Furthermore, matrine enhances the effects of cisplatin, 5-fluorouracil, and paclitaxel in A549 cells, and the anticancer effects exhibit a dosage-dependent manner. In summary, matrine induced cell apoptosis and enhanced the effects of anticancer drugs in NSCLC cells; the mechanism might be associated with the CCR7 signal.

scholarly journals A dose- and time-dependent effect of oxythiamine on cell growth inhibition in non-small cell lung cancer

2021 ◽  
Author(s):  
Lin Bai ◽  
Hui-li Zhu
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Critical Role ◽  
A549 Cells ◽  
Small Cell ◽  
Time Dependent ◽  
Dependent Manner ◽  
Small Cell Lung

AbstractThe high mortality rate of non-small-cell lung cancer (NSCLC) is mostly due to the high risk of recurrence. A comprehensive understanding of proliferation mechanisms of NSCLC would remarkably contribute to blocking up the invasion and metastasis of tumor cells. In our previous study, the remarkable decreased activity of Thiamine-dependent enzymes (TDEs), involving in intermediary metabolism responsible for energy production of tumor, was found under conditions of thiamine deficiency in vivo. To explore the effect of Oxythiamine (OT), a TDEs antimetabolite, on cell growth, we co-cultured A549 cells with OT in vitro at various doses (0.1, 1, 10 and 100 μM) and time periods (6, 12, 24 and 48 h) and subsequent cell proliferation and apoptosis assays were performed respectively. Our findings demonstrated that A549 cells proliferation was significantly downregulated by OT treatment in a progressively dose as well as time dependent manner. Inhibition of TDEs resulted in antagonism of lung cancer growth by inducing cells to cease the cycle as well as apoptotic cell death. We concluded a critical role of OT, a TDEs antagonistic compound, indicating the potential target of its practical use.

scholarly journals Up-Regulation of p53/miR-628-3p Pathway, a Novel Mechanism of Shikonin on Inhibiting Proliferation and Inducing Apoptosis of A549 and PC-9 Non–Small Cell Lung Cancer Cell Lines

2021 ◽  
Vol 12 ◽  
Author(s):  
Jieli Pan ◽  
Meiya Li ◽  
Fenglin Yu ◽  
Feiye Zhu ◽  
Linyan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Strategies ◽  
A549 Cells ◽  
Direct Interaction ◽  
Promoter Sequence ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung

Shikonin (SHK) is a pleiotropic agent with remarkable cell growth inhibition activity against various cancer types, especially non–small cell lung cancer (NSCLC), but its molecular mechanism is still unclear. Our previous study found that miR-628-3p could inhibit the growth of A549 cells and induce its apoptosis. Bioinformatics analysis predicted that miR-628-3p promoter sequence contained p53 binding sites. Considering the regulatory effect of SHK on p53, we speculate that SHK may inhibit the growth and induce apoptosis of NSCLC cells by up-regulating miR-628-3p. CCK-8 and EdU assay confirmed the inhibitory effect of SHK on A549 and PC-9 cells. Meanwhile, quantitative reverse transcription–polymerase chain reaction and Western blot showed that SHK could promote the expression of p53 and miR-628-3p in a dose-dependent manner. Overexpression of p53 or miR-628-3p can inhibit the growth and promote apoptosis of A549 and PC-9 cells, while silencing p53 or miR-628-3p has the opposite effect. Dual luciferase reporting assay and ChIP (chromatin immunoprecipitation) assay further verified the direct interaction between p53 and the promoter of miR-628-3p. Gene knockdown for p53 or miR-628-3p confirmed that SHK inhibits the growth and induces apoptosis of A549 and PC-9 cells at least partly by up-regulating p53/miR-628-3p signaling pathway. Therefore, these novel findings provide an alternative approach to target p53/miR-628-3p axis and could be used for the development of new treatment strategies for NSCLC.

scholarly journals Dehydroeffusol inhibits hypoxia-induced epithelial–mesenchymal transition in non-small cell lung cancer cells through the inactivation of Wnt/β-catenin pathway

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Haitao Wei ◽  
Feng Zhang ◽  
Jiali Wang ◽  
Min Zhao ◽  
Tao Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Normoxic Condition ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Abstract Dehydroeffusol (DHE) is a phenanthrene compound that possesses anti-tumor activity. However, the effect of DHE on non-small cell lung cancer (NSCLC) has not been investigated previously. Therefore, the objective of our study was to explore the role of DHE in NSCLC and the underlying mechanism. Our results showed that DHE significantly inhibited the cell viability of A549 cells in a dose- and time-dependent manner under normoxic condition. Moreover, A549 cells were more sensitive to DHE under hypoxic condition compared with the A549 cells cultured in normoxic condition. Hypoxia-induced increased migration and invasion abilities were mitigated by DHE in A549 cells. Treatment of DHE caused increased E-cadherin expression and decreased N-cadherin expression in hypoxia-induced A549 cells. DHE also suppressed hypoxia-induced increase in both protein and mRNA levels of hypoxia inducible factor-1α (HIF-1α) expression in A549 cells. Furthermore, DHE inhibited hypoxia-induced activation of Wnt/β-catenin pathway in A549 cells. The inhibitory effect of DHE on hypoxia-induced EMT was reversed by LiCl, which is an activator of Wnt/β-catenin signaling pathway. In conclusion, these findings demonstrated that DHE prevented hypoxia-induced EMT in NSCLC cells by inhibiting the activation of Wnt/β-catenin pathway, suggesting that DHE might serve as a therapeutic target for the NSCLC metastasis.

scholarly journals MiR-384 induces apoptosis and autophagy of non-small cell lung cancer cells through the negative regulation of Collagen α-1(X) chain gene

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Qingkui Guo ◽  
Min Zheng ◽  
Ye Xu ◽  
Ning Wang ◽  
Wen Zhao
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Small Cell ◽  
Chain Gene ◽  
Small Cell Lung

AbstractThe present study aims to investigate the mechanism of miR-384 in non-small cell lung cancer (NSCLC) cell apoptosis and autophagy by regulating Collagen α-1(X) chain (COL10A1). Bioinformatics methods were applied to evaluate potential miRNAs and genes that might correlate with NSCLC. Tumor tissues and adjacent tissues from 104 NSCLC patients were collected and human NSCLC A549 cell line was selected for subsequent experiments. A549 cells were treated with miR-384 mimic, miR-384 inhibitor, or knockdown of COL10A1. Quantitative real-time PCR (qRT-PCR) and Western blotting were utilized to detect the levels of miR-384, COL10A, Survivin, Bcl-2, Bax, Bcl-xl, Beclin 1, and LC3 in tissues and cells. A series of biological assays including MTT assay, Annexin V-FITC/PI (propidium iodide) staining, immunofluorescence, monodansylcadaverine (MDC) staining were conducted to investigate the effects of miR-384 and COL10A1 on NSCLC cells. Tumorigenicity assay for nude rats was applied. Results obtained from the present study indicated that miR-384 down-regulated COL10A1 by targetting it. Compared with adjacent tissues, miR-384 expression was obviously reduced while COL10A1 expression was significantly enhanced in NSCLC tissues (all P<0.05). Outcomes in vivo and in vitro suggested that cell proliferation and tumorigenicity were inhibited while cell apoptosis and autophagy were induced in NSCLC cells treated with up-regulation of miR-384 or silence of COL10A1. In miR-384 inhibitor group, cell proliferation was improved, while cell apoptosis was reduced and cell autophagy was decreased whereas tumorigenicity of cells was strengthened. Based on the findings of our study, it was established that miR-384 could down-regulate COL10A1 levels, subsequently inhibiting cell proliferation and promoting cell apoptosis and autophagy in NSCLC cells.

scholarly journals miR-101-3p sensitizes non-small cell lung cancer cells to irradiation

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 413-423
Author(s):  
Zhonghui Li ◽  
Zhenjie Qu ◽  
Ying Wang ◽  
Meilin Qin ◽  
Hua Zhang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Formation Rate ◽  
A549 Cells ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
Survival Fraction

AbstractRecent studies have revealed that microRNAs regulate radiosensitivity of non-small cell lung cancer (NSCLC). The aim of this study was to investigate whether miR-101-3p is correlated with radiosensitivity of NSCLC. According to our results, miR-101-3p was downregulated in NSCLC tissues and cell lines. Moreover, miR-101-3p was decreased in A549 cells’ response to irradiation in a dose-dependent manner. Upregulation of miR-101-3p decreased survival fraction and colony formation rate and increased irradiation-induced apoptosis in irradiation-resistant cells, while miR-101-3p depletion had the opposite effects in irradiation-sensitive cells. Furthermore, mechanistic target of rapamycin (mTOR) is a target gene of miR-101-3p. The expressions of mTOR, p-mTOR, and p-S6 were curbed by overexpression of miR-101-3p in A549R cells, which was enhanced by repression of miR-101-3p in A549 cells. Intriguingly, elevation in mTOR abated miR-101-3p upregulation-induced increase in irradiation sensitivity in irradiation-resistant cell line. In contrast, rapamycin undermined miR-101-3p inhibitor-mediated reduction of irradiation sensitivity in irradiation-sensitive cell line. Besides, miR-101-3p overexpression enhanced the efficacy of radiation in an NSCLC xenograft mouse model. In conclusion, miR-101-3p sensitized A549 cells to irradiation via inhibition of mTOR-signaling pathway.

scholarly journals GDC-0349 inhibits non-small cell lung cancer cell growth

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Han Yang ◽  
Jun Zhao ◽  
Mengjing Zhao ◽  
Lihao Zhao ◽  
Li-na Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Jnk Activation

Abstract Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related human mortality with a clear need for new therapeutic intervention. GDC-0349 is a potent and selective ATP-competitive mTOR inhibitor. In A549 cells and primary human NSCLC cells, GDC-0349 inhibited cell growth, proliferation, cell cycle progression, migration and invasion, while inducing significant apoptosis activation. Although GDC-0349 blocked Akt-mTORC1/2 activation in NSCLC cells, it also exerted cytotoxicity in Akt1-knockout A549 cells. Furthermore, restoring Akt-mTOR activation by a constitutively-active Akt1 only partially attenuated GDC-0349-induced A549 cell apoptosis, indicating the existence of Akt-mTOR-independent mechanisms. In NSCLC cells GDC-0349 induced sphingosine kinase 1 (SphK1) inhibition, ceramide accumulation, JNK activation and oxidative injury. Conversely, N-acetylcysteine, the JNK inhibitor and sphingosine 1-phosphate alleviated GDC-0349-induced NSCLC cell apoptosis. In vivo, daily oral administration of GDC-0349 potently inhibited NSCLC xenograft growth in mice. Akt-mTOR in-activation, SphK1 inhibition, JNK activation and oxidative stress were detected in NSCLC xenograft tissues with GDC-0349 administration. In summary, GDC-0349 inhibits NSCLC cell growth via Akt-mTOR-dependent and Akt-mTOR-independent mechanisms.

scholarly journals Long intergenic noncoding RNA-p21 inhibits apoptosis by decreasing PUMA expression in non-small cell lung cancer

2018 ◽  
Vol 47 (1) ◽  
pp. 481-493 ◽  
Author(s):  
Tao Yang ◽  
Wenjun Zhang ◽  
Li Wang ◽  
Chunyan Xiao ◽  
Bingling Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Noncoding Rna ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Puma Expression ◽  
Long Intergenic Noncoding Rna

Objective Long noncoding RNAs (lncRNAs) are important mediators in tumor progression. Long intergenic noncoding RNA-p21 (lincRNA-p21) participates in multiple biological processes. This study explored the role of lincRNA-p21 in human non-small cell lung cancer (NSCLC) progression and potential regulatory mechanisms. Methods LincRNA-p21 expression in NSCLC tissues and cell lines (A549, H1299, H1650, and NCI-H2087) was determined by quantitative real-time PCR. LincRNA-p21 overexpressing and sh-lincRNA-p21 lentiviral were respectively transfected into H1299 and A549 cells. Flow cytometry was used to measure apoptosis. Microarray analysis and RNA pull-down assay were used to predict the target genes of lincRNA-p21. Finally, PUMA siRNA and overexpressing PUMA were transfected into NSCLC cells, and the extent of cell apoptosis was measured. The protein expression levels of the relative genes were confirmed by western blot analysis. Results LincRNA-p21 was significantly upregulated in NSCLC tissues and cells. The upregulation of lincRNA-p21 considerably inhibited cell apoptosis while the downregulation of lincRNA-p21 showed the opposite effect. PUMA was a direct target gene of lincRNA-p21 and was negatively correlated with lincRNA-p21 in NSCLC specimens. The anti-apoptotic effect of lincRNA-p21 can be effectively attenuated by the upregulation of PUMA. Conclusion LincRNA-p21 is aberrantly upregulated in NSCLC and inhibits cell apoptosis by decreasing PUMA expression.

scholarly journals Degradation of Mcl-1 through GSK-3β Activation Regulates Apoptosis Induced by Bufalin in Non-Small Cell Lung Cancer H1975 Cells

2017 ◽  
Vol 41 (5) ◽  
pp. 2067-2076 ◽  
Author(s):  
Xiao-hong Kang ◽  
Jing-hang Zhang ◽  
Qing-qin Zhang ◽  
Yan-hui Cui ◽  
Ying Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Cell Counting ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
Gsk 3Β ◽  
Induced Apoptosis

Background/Aims: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. Methods: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting. The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation assay. Results: Cell growth was inhibited by bufalin in a time and dose-dependent manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA expression in H1975 cells, but strongly promoted Mcl-1 protein degradation. Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect NOXA protein levels, but downregulated the expression of p-GSK-3β. GSK-3 inhibitor and GSK-3β siRNA resulted in increased levels of Mcl-1 and reversed the bufalin-induced Mcl-1 degradation. Conclusion: Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3β activation was involved in bufalin-induced apoptosis.

Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

2020 ◽  
Vol 20 (8) ◽  
pp. 982-988 ◽  
Author(s):  
Le-Le Zhang ◽  
Han Bao ◽  
Yu-Lian Xu ◽  
Xiao-Ming Jiang ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Biological Activities ◽  
A549 Cells ◽  
Immunofluorescence Assay ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

scholarly journals Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Sun ◽  
Jing Chen ◽  
Xuechao Sun ◽  
Guonian Wang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Cisplatin Sensitivity

Abstract Backgrounds As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms. Methods We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues. Results The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells. Conclusions Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

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