scholarly journals Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Wu ◽  
Ru Chen ◽  
Huiqing Shen ◽  
Ting Yan ◽  
Yu Qian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Mapk Signaling ◽  
Small Cell ◽  
Sequencing Data ◽  
Small Cell Lung ◽  
Invasion And Migration

Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth in vivo. We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-β signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.

scholarly journals Rosmarinic acid reverses non‐small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway

2020 ◽  
Vol 34 (5) ◽  
pp. 1142-1153 ◽  
Author(s):  
Xiao‐Zhong Liao ◽  
Ying Gao ◽  
Ling‐Ling Sun ◽  
Jia‐Hui Liu ◽  
Han‐Rui Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Rosmarinic Acid ◽  
Cisplatin Resistance ◽  
Mapk Signaling ◽  
Small Cell ◽  
Mapk Signaling Pathway ◽  
Small Cell Lung

Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway

Tumor Biology ◽  
2016 ◽  
Vol 37 (7) ◽  
pp. 9615-9624 ◽  
Author(s):  
Kyoung Ah Kang ◽  
Mei Jing Piao ◽  
Susara Ruwan Kumara Madduma Hewage ◽  
Yea Seong Ryu ◽  
Min Chang Oh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Mapk Signaling ◽  
Small Cell ◽  
Mapk Signaling Pathway ◽  
Small Cell Lung

scholarly journals Aspirin potentiates celecoxib-induced growth inhibition and apoptosis in human non-small cell lung cancer by targeting GRP78 activity

2020 ◽  
Vol 12 ◽  
pp. 175883592094797
Author(s):  
Xiangyu Zhang ◽  
Jia Chen ◽  
Cheng Cheng ◽  
Ping Li ◽  
Fangfang Cai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Body Weight ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Mapk Signaling ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Background: Aspirin has recently emerged as an anticancer drug, but its therapeutic effect on lung cancer has been rarely reported, and the mechanism of action is still unclear. Long-term use of celecoxib in large doses causes serious side effects, and it is necessary to explore better ways to achieve curative effects. In this study, we evaluated the synergistic anticancer effects of celecoxib and aspirin in non-small cell lung cancer (NSCLC) cells. Methods: In vitro, we evaluated the combined effects of celecoxib (40 μM) and aspirin (8 mM) on cell apoptosis, cell cycle distribution, cell proliferation, cell migration and signaling pathways. Furthermore, the effect of aspirin (100 mg/kg body weight) and celecoxib (50 mg/kg body weight) on the growth of xenograft tumors was explored in vivo. Results: Our data suggest that cancer sensitivity to combined therapy using low concentrations of celecoxib and aspirin was higher than that of celecoxib or aspirin alone. Further research showed that the anti-tumor effect of celecoxib combined with aspirin was mainly produced by activating caspase-9/caspase-3, arresting cell cycle and inhibiting the ERK-MAPK signaling pathway. In addition, celecoxib alone or in combination with aspirin inhibited the migration and invasion of NSCLC cells by inhibiting MMP-9 and MMP-2 activity levels. Moreover, we identified GRP78 as a target protein of aspirin in NSCLC cells. Aspirin induced an endoplasmic reticulum stress response by inhibiting GRP78 activity. Furthermore, combination therapy also exhibited a better inhibitory effect on tumor growth in vivo. Conclusions: Our study provides a rationale for further detailed preclinical and potential clinical studies of the combination of celecoxib and aspirin for NSCLC therapy.

scholarly journals MEK inhibitors for the treatment of non-small cell lung cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Han ◽  
Yang Liu ◽  
Sen Yang ◽  
Xuan Wu ◽  
Hongle Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Mapk Signaling ◽  
Small Cell ◽  
Erk Signaling ◽  
Therapeutic Effects ◽  
Small Cell Lung ◽  
Mek Inhibitors

AbstractBRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They lead to the proliferation, differentiation, and apoptosis of tumor cells by activating the RAS/RAF/MEK/ERK signaling pathway. To date, agents that target RAS/RAF/MEK/ERK signaling pathway have been investigated in NSCLC patients harboring BRAF mutations. BRAF and MEK inhibitors have gained approval for the treatment of patients with NSCLC. According to the reported findings, the combination of MEK inhibitors with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase inhibitors or BRAF inhibitors is highly significant for improving clinical efficacy and causing delay in the occurrence of drug resistance. This review summarized the existing experimental results and presented ongoing clinical studies as well. However, further researches need to be conducted to indicate how we can combine other drugs with MEK inhibitors to significantly increase therapeutic effects on patients with lung cancer.

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