ReferenceID 1084

Acetylshikonin exerts anti-tumor effects on non-small cell lung cancer through dual inhibition of STAT3 and EGFR

Phytomedicine

Background: Lung cancer is one of the most common types of malignant tumor. It has one of the highest morbidity and mortality rates worldwide, and approximately 85% of cases are non-small cell lung cancer (NSCLC). Clinic

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Reference Id
1084
Evidence Id
17674
Core Evidence Id
17674
Source Reference Id
2154
Herb2 Reference Id
HBREF002951
Subject Paper Key
HBIN014493_35526322
Pubmed Id
35526322
Doi
10.1016/j.phymed.2022.154109
Paper Title
Acetylshikonin exerts anti-tumor effects on non-small cell lung cancer through dual inhibition of STAT3 and EGFR
Paper Abstract
Background: Lung cancer is one of the most common types of malignant tumor. It has one of the highest morbidity and mortality rates worldwide, and approximately 85% of cases are non-small cell lung cancer (NSCLC). Clinically, several EGFR inhibitors have been used to treat NSCLC, but resistance can develop. Studies have shown that cross talk between signal transducer and activator of transcription 3 (STAT3) and epidermal growth factor receptor (EGFR) can mediate drug resistance. Acetylshikonin has obvious antitumor effects, but the mechanism of action is still unclear. Purpose: To analyze the antitumor activity of acetylshikonin in lung cancer and clarify its molecular mechanism. Methods: Methyl thiazolyl tetrazolium (MTT), colony formation and 5-ethynyl-2'-deoxyuridine (EDU) assays were performed to examine the effects of acetylshikonin in inhibiting the proliferation of NSCLC cells (PC-9, H1975 and A549). Scratch wound and transwell assays were used to evaluate the migration and invasion of NSCLC cells. Flow cytometry was employed to determine whether acetylshikonin could induce apoptosis. Proteome sequencing was used to identify the targets of acetylshikonin. Immunofluorescence staining and western blotting were utilized to verify the inhibition of STAT3 and EGFR phosphorylation. A xenotransplantation model was established to evaluate the efficacy of acetylshikonin in nude mice. Results: Our data demonstrated that acetylshikonin significantly decreased the survival rate of human NSCLC cells, increased the apoptotic rate and inhibited cell migration dose-dependently. Immunofluorescence staining and western blotting analyses revealed that acetylshikonin inhibited EGFR and STAT3 pathways. Acetylshikonin also inhibited tumor growth in a xenograft model better than inhibitors of EGFR and STAT3. Conclusion: Acetylshikonin has anti-cancer effects on NSCLC cells by inhibiting EGFR and STAT3, indicating that acetylshikonin may be a new antitumor drug to treat NSCLC.
Journal
Phytomedicine
Publish Year
2022
Experiment Subject
mouse; human; nsclc cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Tumor; Malignant Tumor; Non-small Cell Lung Cancer; Lung Cancer
Paper Title Cn
Paper Title En
Acetylshikonin exerts anti-tumor effects on non-small cell lung cancer through dual inhibition of STAT3 and EGFR
Bilingual Status
semi_complete