scholarly journals Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zhiqiang Wu ◽  
Bin Xu ◽  
Zhiyi Yu ◽  
Qin He ◽  
Zhuyuan Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathways ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stat3 Signaling ◽  
Induced Apoptosis ◽  
Gefitinib Resistance

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.

scholarly journals FGL1 Regulates Acquired Resistance to Gefitinib by Inhibiting Apoptosis in Non-small Cell Lung Cancer

2020 ◽  
Author(s):  
Cuilan Sun ◽  
Weiwei Gao ◽  
Jiatao Liu ◽  
Hao Cheng ◽  
Jiqing Hao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Nsclc Cell ◽  
Nsclc Cell Line ◽  
Small Cell Lung ◽  
Gefitinib Resistance

Abstract Background: This study investigated the role of fibrinogen-like protein 1 (FGL1) in regulating gefitinib resistance of PC9/GR non-small cell lung cancer (NSCLC). Methods: The effect of different concentrations of gefitinib on cell proliferation were evaluated using the CCK-8 assay. FGL1 expression in the normal human bronchial epithelial cell line Beas-2B, as well as four lung tumor cell lines, H1975, A549, PC9, and PC9/GR, was investigated by using western blotting and qRT-PCR. FGL1 was knocked down using small interfering RNA to evaluate the effects of FGL1 on PC9 and PC9/GR. The correlation between FGL1 expression and gefitinib resistance was determined in vitro via CCK-8 and colony formation assays, and flow cytometry and in vivo via flow cytometry and immunohistochemistry. Results: FGL1 expression was significantly upregulated in non-small cell lung cancer cells with EGFR mutation and higher in the gefitinib-resistant NSCLC cell line PC9/GR than in the gefitinib-sensitive NSCLC cell line PC9. Further, FGL1 expression in PC9 and PC9/GR cells increased in response to gefitinib treatment in a dose-dependent manner. Knockdown of FGL1 suppressed cell viability, reduced the gefitinib IC50 value, and enhanced apoptosis in PC9 and PC9/GR cells upon gefitinib treatment. Mouse xenograft experiments showed that FGL1 knockdown in PC9/GR tumor cells enhanced the inhibitory and apoptosis-inducing actions of gefitinib. The potential mechanism of gefitinib in inducing apoptosis of PC9/GR cells involves inhibition of PARP1 and caspase 3 expression via suppression of FGL1.Conclusions: FGL1 confers gefitinib resistance in the NSCLC cell line PC9/GR by regulating the PARP1/caspase 3 pathway. Hence, FGL1 is a potential therapeutic target to improve the treatment response of NSCLC patients with acquired resistance to gefitinib.

scholarly journals FGL1 Regulates Acquired Resistance to Gefitinib by Inhibiting Apoptosis in Non-small Cell Lung Cancer

2020 ◽  
Author(s):  
Cuilan Sun ◽  
Weiwei Gao ◽  
Jiatao Liu ◽  
Hao Cheng ◽  
Jiqing Hao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Nsclc Cell ◽  
Nsclc Cell Line ◽  
Small Cell Lung ◽  
Gefitinib Resistance

Abstract Background: This study investigated the role of fibrinogen-like protein 1 (FGL1) in regulating gefitinib resistance of PC9/GR non-small cell lung cancer (NSCLC). Methods: The effect of different concentrations of gefitinib on cell proliferation were evaluated using the CCK-8 assay. FGL1 expression in the normal human bronchial epithelial cell line Beas-2B, as well as four lung tumor cell lines, H1975, A549, PC9, and PC9/GR, was investigated by using western blotting and qRT-PCR. FGL1 was knocked down using small interfering RNA to evaluate the effects of FGL1 on PC9 and PC9/GR. The correlation between FGL1 expression and gefitinib resistance was determined in vitro via CCK-8 and colony formation assays, and flow cytometry and in vivo via flow cytometry and immunohistochemistry.7 Results: FGL1 expression was significantly upregulated in non-small cell lung cancer cells with EGFR mutation and higher in the gefitinib-resistant NSCLC cell line PC9/GR than in the gefitinib-sensitive NSCLC cell line PC9. Further, FGL1 expression in PC9 and PC9/GR cells increased in response to gefitinib treatment in a dose-dependent manner. Knockdown of FGL1 suppressed cell viability, reduced the gefitinib IC50 value, and enhanced apoptosis in PC9 and PC9/GR cells upon gefitinib treatment. Mouse xenograft experiments showed that FGL1 knockdown in PC9/GR tumor cells enhanced the inhibitory and apoptosis-inducing actions of gefitinib. The potential mechanism of gefitinib in inducing apoptosis of PC9/GR cells involves inhibition of PARP1 and caspase 3 expression via suppression of FGL1.Conclusions: FGL1 confers gefitinib resistance in the NSCLC cell line PC9/GR by regulating the PARP1/caspase 3 pathway. Hence, FGL1 is a potential therapeutic target to improve the treatment response of NSCLC patients with acquired resistance to gefitinib.

MiR-189 Exerts Anticancer Activity Through Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) Pathway in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 (12) ◽  
pp. 2421-2426
Author(s):  
Hongyun Ji ◽  
Hui Lu ◽  
Feng Li ◽  
Ying Qu ◽  
Qing Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Janus Kinase ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Stat3 Signaling ◽  
Induced Apoptosis

Non-small cell lung cancer (NSCLC) remains a threat to human health but its etiology remains unclear. MicroRNAs (miRNAs) are involved in NSCLC progression. This study aims to elucidate the mechanism by how exosomal miR-189 functions in NSCLC. After identification, BMSCs were co-cultured with NSCLC cells which were then transfected with miR-189 mimics followed by analysis of the expression of JAK2/Stat3 proteins and miR-189, cell migration and invasion by Transwell assay, cell viability by MTT assay, apoptosis by flow cytometry. miR-189 is downregulated in NSCLC cells and tissues. miR-189 overexpression inhibited the phosphorylation of JAK2/Stat3 and suppressed malignant characteristics of cancer cells and induced apoptosis. Co-culture with BMSCs and NSCLC cells elevated miR-189 level and inactivated JAK2/STAT3 signaling, thereby suppressing malignant characteristics of cancer cells. In conclusion, BMSCs carrying miR-189 restrain NSCLC progression by blocking JAK2/STAT3 signaling, which may help development of gene therapy for NSCLC.

scholarly journals Genome-wide profiling of micro-RNA expression in gefitinib-resistant human lung adenocarcinoma using microarray for the identification of miR-149-5p modulation

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769165 ◽  
Author(s):  
Yong Hu ◽  
Xiaobing Qin ◽  
Dali Yan ◽  
Haixia Cao ◽  
Leilei Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Micro Rna ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Gefitinib Resistance

To understand the mechanism involved in gefitinib resistance, we established gefitinib-resistant human HCC827/GR-8-1 cell line from the parental HCC827 cell line. We compared the micro-RNA expression profiles of the HCC827 cells HCC827/GR-8-1 using Agilent micro-RNA microarrays. The micro-RNAs, such as the miR-149-5p, were up- or downregulated and associated with acquired gefitinib resistance. Quantitative real-time polymerase chain reaction was then performed to verify the expression patterns of different micro-RNAs. The result showed that miR-149-5p was upregulated in the HCC827/GR-8-1 cell line. To investigate the biological function of miR-149-5p in non–small cell lung cancer cells acquired gefitinib resistance, we examined cell proliferation using a cell counting kit-8 assay. Cell viability was evaluated after the miR-149-5p mimics, inhibitors, and negative control were separately transfected into the non–small cell lung cancer cells. The results showed that the non–small cell lung cancer cells transfected with miR-149-5p mimics exhibited reduced cell motility. The drug-sensitivity assay results revealed that the overexpression of miR-149-5p effectively evaluates the half maximal inhibitory concentration values of the cell in response to gefitinib, and the downregulation of miR-149-5p can attenuate the half maximal inhibitory concentration values of the cell lines in response to gefitinib. Furthermore, the levels of miR-149-5p in the HCC827 and HCC827/GR-8-1 cells were inversely correlated with caspase-3 expression. In conclusion, this study revealed that miR-149-5p is upregulated in the HCC827/GR-8-1 cells and involved in the acquired gefitinib resistance.

Chitosan Nano-encapsulation Enhances Gedunin Cytotoxicity A gainst Human Non-small-cell Lung Cancer (NCI-H292) Cell Line

2017 ◽  
Vol 7 (3) ◽  
Author(s):  
Chukwumaobim D.U. Nwokwu ◽  
Sameera R. Samarakoon ◽  
Desiree N. Karunaratne ◽  
Nuwanthi P. Katuvawila ◽  
Meran K. Ediriweera ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals SCLC-J1, a novel small cell lung cancer cell line

2021 ◽  
Vol 27 ◽  
pp. 101089
Author(s):  
Kazuo Ohara ◽  
Shintaro Kinoshita ◽  
Jun Ando ◽  
Yoko Azusawa ◽  
Midori Ishii ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cell Lung Cancer ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung
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