Synergistic Antitumor Effect of Genitinib (Iressa®) with Flavonoids from the Scutellaria baicalensis Root on the Non-Small Cell Lung Cells

2017 ◽  
Vol 10 (1) ◽  
pp. 62-69
Author(s):  
Y. Hirata ◽  
M. Tatsu ◽  
C. Amano ◽  
Y. Kawaratani ◽  
M. Hirata ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Remission Rate ◽  
Cell Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Scutellaria Baicalensis ◽  
Wild Type ◽  
Post Translational Modification ◽  
Small Cell Lung ◽  
Oroxylin A

Background: As was reported, gefitinib (Iressa®) showed a strong growth inhibitory effect on non-small-cell lung cancer PC-9 cells with mutant EGFR, but did not so much on A549 cells with wild-type EGFR. Observation: We here demonstrated by isobolograms and combination index analyses that the paired combinations of gefitinib with flavonoids from Wogon (Scutellaria baicalensis root): wogonin, oroxylin A and chrysin exerted synergistic anti-tumor effects against A549 cells. Result: The cell cycle analyses revealed that the combination of gefitinib and oroxylin A in A549 cells induced more apoptotic cells than other paired combinations as well as gefitinib alone. Thus, it is anticipated that oroxylin A could help to enhance the remission rate in the gefitinib therapy for the patients with non-small cell cancer cells with wild-type EGFR which provide a poor prognosis. Conclusion: Since the Wogon flavonoids, wogonin, oroxylin A and chrysin, accelerated the acetylation of Lysine residues of histone proteins, it is suggested that they put forth anti-tumor activities through inhibition of histone deacetylases which mediated the post-translational modification of histones.

A Case of EGFR-wild-type Adenocarcinoma of Recurrent Non-small Cell Lung Cancer Responding to Erlotinib

Haigan ◽  
2012 ◽  
Vol 52 (3) ◽  
pp. 315-319
Author(s):  
Masami Morimoto ◽  
Naoki Hino ◽  
Hisashi Matsuoka ◽  
Takanori Miyoshi ◽  
Masaru Tsuyuguchi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung

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.

Successful treatment of pulmonary lymphangitic carcinomatosis by anlotinib in 14 Chinese patients with advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21064-e21064
Author(s):  
Shencun Fang ◽  
Wanwan Cheng ◽  
Yingming Zhang ◽  
Haitao Zhang ◽  
Si Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lymphatic Metastasis ◽  
Small Cell ◽  
Smoking History ◽  
Wild Type ◽  
Small Cell Lung ◽  
The Impact ◽  
Lymphangitic Carcinomatosis

e21064 Background: Pulmonary lymphangitic carcinomatosis (PLC) occurs in 6%-8% of intrathoracic metastases among malignant tumor. The median survival was only 2.0 months from time of pulmonary symptoms to death in cases during 2000-2018, which is a poor prognosis. Effective interventions were needed besides standard chemotherapy and symptomatic support. Anlotinib showed a critical effect on lymphangiogenesis, and lymphatic metastasis in mouse models of lung adenocarcinoma, it might be a therapeutic option for tumor lymphatic metastasis. In this study, we retrospectively analyzed the efficacy and safety of anlotinib for PLC in patients with Non-small Cell Lung Cancer (NSCLC). Methods: We retrospectively investigated NSCLC patients with PLC at our hospital between May 2018 and November 2020, who received anlotinib monotherapy or combined therapy for PLC. Data were analyzed for progression-free survival (PFS), overall survival (OS), objective response rate(ORR), disease control rate(DCR) and adverse events (AE). The impact of clinical and genomic factors on PFS and OS were also assessed. Results: A total of 14 patients were enrolled with a median age of 64 years. 10(71.4%) were male, 4(28.6%) has smoking history, 10(71.4%) of patients had a performance status of 2-3. 9, 3, 2 patients had TP53 mutation, EGFR mutation, ALK fusion respectively. 9(64.3%) patients received anlotinib monotherapy. Of 14 patients, 8 achieved partial response (PR), 5 presented stable disease (SD), 1 had progressed disease. The ORR and DCR were 57.1% and 92.9% respectively. The median PFS was 3.1 months (95% CI: 2.0-4.2), the median OS for 1, 2, ≥3 line were 13 months, 7.2 months, 5.2 months, respectively. Median PFS and OS (≥3 line) were significantly longer for patients with TP53-mutant tumors compared with those with TP53–wild-type tumors (median PFS: 7 vs. 1.1 months, median OS (≥3 line): 6.8 vs. 1.9 months). No difference of PFS and OS (≥3 line) was found between EGFR or ALK alteration and the corresponding wild type patients. The most frequently reported AEs were high blood pressure (11, 78.6%), hand foot syndrome (6, 42.9%), diarrhea (5, 35.7%), fatigue (4, 28.6%), hoarseness (3, 21.4%), proteinuria (2, 14.3%) and stomatitis (2, 14.3%). Conclusions: Anlotinib presented favorable efficacy in patients with pulmonary lymphangitic carcinomatosis and conferred considerable survival benefit compared with previous studies, especially in patients harboring TP53 mutations. The AEs were manageable. These indicated that anlotinib can be a promising therapeutic treatment of PLC. More clinical data is needed to validate this finding.

scholarly journals Combination of baicalein and docetaxel additively inhibits the growth of non-small cell lung cancer in vivo

2018 ◽  
Vol 01 (03) ◽  
pp. 213-218 ◽  
Author(s):  
Linwei Lu ◽  
Zhengxiao Zhao ◽  
Lumei Liu ◽  
Weiyi Gong ◽  
Jingcheng Dong
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Bearing ◽  
Liver And Kidney ◽  
To Receive

Objective: The objective of this study is to preliminarily evaluate the efficacy of the combination of baicalein and docetaxel on non-small cell lung cancer (NSCLC) in vivo. Methods: The subcutaneous model was established by inoculation of A549 cells, and then these tumor-bearing mice were randomly assigned to eight groups to receive normal saline (NS) as control, baicalein alone, Taxotere[Formula: see text] (docetaxel injection) alone or the combination of baicalein and Taxotere[Formula: see text]. The effect of the combination treatment was evaluated by [Formula: see text] value. Tumors were harvested for TUNEL and CD31 immunohistochemical staining and important organs for H&E staining. Results: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg significantly reduced tumor weight and inhibited the growth rate of tumor, displaying the additive effect indicated by the [Formula: see text] value. Increased apoptosis and decreased tumor angiogenesis also provided pathological evidence. Additionally, baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg did not increase toxicity in lung, liver and kidney. Conclusion: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg additively inhibits the growth of NSCLC in vivo, and the mechanism underlying remains to be discovered.

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