scholarly journals Sijunzi Tang Enhances The Sensitivity of Lung Cancer Cells To Gefitinib Based On Glutamine Metabolism

2021 ◽  
Author(s):  
Zhihong Wang ◽  
Shiyuan Wang ◽  
Xia Liu ◽  
Bo Cao ◽  
Mingyu Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Kinase Inhibitors ◽  
Combined Treatment ◽  
Acquired Resistance ◽  
Complementary Therapy ◽  
Glutamine Metabolism ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Egfr Tkis

Abstract Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been the major bottleneck that limits the long-term clinical efficacy. Therefore, the exploration of novel strategies for the treatment of non-small cell lung cancer (NSCLC) is urgent. Sijunzi Tang (SJZ) has been usually used as a complementary therapy for cancer patients that can prolong their overall life. Nevertheless, its underlying mechanism when combined with EGFR-TKIs is not clear. Methods: Here, the anti-tumor activity was evaluated by determining cell viability by using the Cell Counting Kit-8 (CCK-8). A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to simultaneously quantify nine metabolites in the glutamine metabolic pathway, such as glutamine, glutamate, αketoglutaric acid, fumarate, succinate, citrate, cis-aconitate, alanine, and malate in PC-9/GR cells. Results: The results showed that SJZ could enhance the sensitivity of lung cancer cells to gefitinib. The content of glutamine and glutamate in the SJZ/gefitinib group was significantly lower than that in the gefitinib group, while the concentration of other metabolites did not change significantly. Conclusion: In summary, SJZ can reverse gefitinib resistance by modulating glutamine metabolism. Our results suggested that SJZ might be a potential resistance reversal herbal medicine and combined with gefitinib might be a promising strategy for the therapy of lung cancer. Also, the research will provide novel insights for the study of the mechanisms on Traditional Chinese medicine (TCM) prescriptions-reversed resistance of EGFR-TKIs, and scientific basis for the combined treatment of lung cancer with TCM and EGFR-TKIs.

scholarly journals Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma

2019 ◽  
Vol 20 (5) ◽  
pp. 1125 ◽  
Author(s):  
Sakhawat Ali ◽  
Muhammad Tahir ◽  
Aamir Khan ◽  
Xue Chen ◽  
Ma Ling ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Combined Treatment ◽  
Acquired Resistance ◽  
Chemotherapy Resistance ◽  
Chemotherapeutic Agents ◽  
Lung Cancer Cells ◽  
Advanced Lung Cancer ◽  
Mesenchymal Transition ◽  
Conditionally Replicating Adenovirus

Cisplatin is ranked as one of the most powerful and commonly prescribed anti-tumor chemotherapeutic agents which improve survival in many solid tumors including non-small cell lung cancer. However, the treatment of advanced lung cancer is restricted due to chemotherapy resistance. Here, we developed and investigated survivin promoter regulating conditionally replicating adenovirus (CRAd) for its anti-tumor potential alone or in combination with cisplatin in two lung cancer cells, H23, H2126, and their resistant cells, H23/CPR, H2126/CPR. To measure the expression of genes which regulate resistance, adenoviral transduction, metastasis, and apoptosis in cancer cells, RT-PCR and Western blotting were performed. The anti-tumor efficacy of the treatments was evaluated through flow cytometry, MTT and transwell assays. This study demonstrated that co-treatment with cisplatin and CRAd exerts synergistic anti-tumor effects on chemotherapy sensitive lung cancer cells and monotherapy of CRAd could be a practical approach to deal with chemotherapy resistance. Combined treatment induced stronger apoptosis by suppressing the anti-apoptotic molecule Bcl-2, and reversed epithelial to mesenchymal transition. In conclusion, cisplatin synergistically increased the tumor-killing of CRAd by (1) increasing CRAd transduction via enhanced CAR expression and (2) increasing p53 dependent or independent apoptosis of lung cancer cell lines. Also, CRAd alone proved to be a very efficient anti-tumor agent in cancer cells resistant to cisplatin owing to upregulated CAR levels. In an exciting outcome, we have revealed novel therapeutic opportunities to exploit intrinsic and acquired resistance to enhance the therapeutic index of anti-tumor treatment in lung cancer.

AMD3100-tagged nano-gold as a targeting nanocarrier for delivery of doxorubicin into lung cancer cells

2021 ◽  
Vol 11 (5) ◽  
pp. 618-626
Author(s):  
Yali Liu ◽  
Changpeng Hu ◽  
Min Zhou ◽  
Qian Zhang ◽  
Qin Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Acquired Resistance ◽  
Lung Cancer Cells ◽  
Cxcr4 Antagonist ◽  
Au Nps ◽  
Nano Gold ◽  
Dependent Model ◽  
Doxorubicin Release

Doxorubicin (DOX) is widely used as a traditional chemotherapy drug in tumor treatment, but its dose-dependent side effects make it susceptible to acquired resistance. CXCR4 is a chemokine receptor that has high expression in many cancers, including lung cancer. In this work, we studied the possibility of using CXCR4 antagonist, AMD3100, as a targeting molecule to targeted delivery of DOX to CXCR4 expressing lung cancer cells through conjugated gold nanoparticles (Au NPs). DOX was intercalated inside the pH-responsive doublestrand DNA (dsDNA) and then conveniently loaded onto the Au NPs. The CXCR4 antagonist, AMD3100, was bonded with LA-PEG, and then conjugated to the surface of Au-S bond. The doxorubicin release from AuNPs@DOX@AMD3100 NPs was in a pH-dependent model, and specificity of AuNPs@DOX@AMD3100 nanoparticle was verified by using free DOX and Au@DOX NPs as control. Results in this work not only confirmed the possibility of using AMD3100 as a targeting ligand for tumor-targeted treatment, but also suggested that the non-toxic Au NPs is a prospect nanocarrier for target design of cancer therapy.

scholarly journals Tumor immune microenvironment in non-small cell lung cancer with EGFR mutation before and after EGFR-TKIs treatment

2021 ◽  
Author(s):  
chao wang ◽  
lihui liu ◽  
sini li ◽  
hua bai ◽  
jie wang
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Treatment Time ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Before And After ◽  
Almost All ◽  
Egfr Tkis

Lung cancer is the most common cancer and a leading cause of death from cancer in men and women in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are considered as the first-line treatment of EGFR mutated NSCLC. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, with a median PFS of 9-14 months. With the development of immunotherapy, people realize that the interaction between tumor immune microenvironment (TIME) and tumor cells can also affect EGFR-TKIs treatment. TIME contains a variety of elements and previous researches of TIME in EGFR-TKIs therapy on NSCLC are decentralized. Here, we review the characteristics of TIME in NSCLC from EGFR-TKIs therapy and its role in TKIs resistance.

scholarly journals Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Dakai Xiao ◽  
Jiaxi He ◽  
Zhihua Guo ◽  
Huiming He ◽  
Shengli Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Glutamine Synthetase ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Clinical Sample ◽  
Glutamine Metabolism ◽  
Lung Cancer Cells ◽  
Mesenchymal Transformation ◽  
Proliferation And Invasion

IntroductionRHPN2, a member of rhophilin family of rho-binding proteins, regulates actin cytoskeleton and vesicular trafficking, and promotes mesenchymal transformation in cancer. We have found that RHPN2 was significantly mutated in lung adenocarcinoma (LUAD). However, the role of RHPN2 in lung cancer is not fully understood.MethodsIn the present study, we investigated the expression of RHPN2 in 125 patients with LUAD by qRT-PCR and correlated its expression with clinical characteristics. The effects of RHPN2 on the proliferation and invasion of lung cancer cells were determined by CCK-8 and in vitro transwell assays, clonogenic assay, and xenograft mouse model. The RhoA pull down assay and Western blotting were performed to elucidate the mechanism of RNPN2 in tumorigenesis of lung cancer.ResultsRHPN2 was overexpressed in tumors from LUAD, and high levels of RHPN2 were associated with poor prognosis of LUAD patients. RHPN2 was required for proliferation and invasion of lung cancer cells. Intriguingly, overexpression of RHPN2 conferred the resistance to glutamine depletion in lung cancer cells. Mechanistic studies revealed that ectopic overexpression of RHPN2 promoted the stability of c-Myc protein via phosphorylation at Ser62 and increased c-Myc target glutamine synthetase (GS). Analysis of GS expression in clinical sample showed that the expression of GS was elevated in tumor cells. Kaplan-Meier analysis revealed that high levels of GS were significantly associated with worse overall survival time of the patients with LUAD.ConclusionsTaken together, this study suggested that RHPN2 was involved in tumorigenesis of lung cancer via modulating c-Myc stability and the expression of its target GS in lung adenocarcinoma, which links RHPN2 and glutamine metabolism.

scholarly journals Elevated Cellular PD1/PD-L1 Expression Confers Acquired Resistance to Cisplatin in Small Cell Lung Cancer Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162925 ◽  
Author(s):  
Fei Yan ◽  
Jiuxia Pang ◽  
Yong Peng ◽  
Julian R. Molina ◽  
Ping Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung

scholarly journals Glutamine Addiction and Therapeutic Strategies in Lung Cancer

2019 ◽  
Vol 20 (2) ◽  
pp. 252 ◽  
Author(s):  
Karolien Vanhove ◽  
Elien Derveaux ◽  
Geert-Jan Graulus ◽  
Liesbet Mesotten ◽  
Michiel Thomeer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Tricarboxylic Acid Cycle ◽  
Treatment Options ◽  
Redox Homeostasis ◽  
Glutamine Metabolism ◽  
Lung Cancer Cells ◽  
Production Networks ◽  
Tricarboxylic Acid Cycle Intermediates

Lung cancer cells are well-documented to rewire their metabolism and energy production networks to support rapid survival and proliferation. This metabolic reorganization has been recognized as a hallmark of cancer. The increased uptake of glucose and the increased activity of the glycolytic pathway have been extensively described. However, over the past years, increasing evidence has shown that lung cancer cells also require glutamine to fulfill their metabolic needs. As a nitrogen source, glutamine contributes directly (or indirectly upon conversion to glutamate) to many anabolic processes in cancer, such as the biosynthesis of amino acids, nucleobases, and hexosamines. It plays also an important role in the redox homeostasis, and last but not least, upon conversion to α-ketoglutarate, glutamine is an energy and anaplerotic carbon source that replenishes tricarboxylic acid cycle intermediates. The latter is generally indicated as glutaminolysis. In this review, we explore the role of glutamine metabolism in lung cancer. Because lung cancer is the leading cause of cancer death with limited curative treatment options, we focus on the potential therapeutic approaches targeting the glutamine metabolism in cancer.

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