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- Title
Arteannuin B Enhances the Effectiveness of Cisplatin in Non-Small Cell Lung Cancer by Regulating Connexin 43 and MAPK Pathway.
- Authors
Huang, Weijuan; Wang, Yanqing; He, Tingsha; Zhu, Jianhua; Li, Jianhuan; Zhang, Sirui; Zhu, Yong; Xu, Yafang; Xu, Lv; Wang, Haoran; Yu, Rongmin; Song, Liyan
- Abstract
Cisplatin (DDP)-based chemotherapy is the first-line regimen for advanced non-small cell lung cancer (NSCLC) patients. However, advanced NSCLC patients may have innate resistance to DDP or develop resistance during DDP treatment. We investigated a natural compound, arteannuin B (Art B), for its potential effects on DDP resistance in NSCLC. Art B was isolated from Artemisia annua by chromatographic purification and spectral elucidation. The activities of Art B on DDP-mediated effects were examined using in vitro and in vivo assays. We observed significant correlations in T stage, clinical stage, chemotherapy resistance and poor survival of NSCLC patients with low Cx43 expression. Art B enhanced the effectiveness of cisplatin by increasing Cx43 expression in normal and DDP-resistant NSCLC cells. Art B also increased DDP uptake through up-regulating Cx43. The combination of DDP and Art B showed better therapeutic effect than individual treatments both in vitro and in vivo. Art B increased intracellular Fe 2 + level, promoted calcium influx, and activated gap junction and MAPK pathways, which might contribute to Art B-mediated effects. Art B may serve as a new drug candidate to enhance the antitumor effect of DDP on NSCLC.
- Subjects
LUNG cancer prognosis; LUNG cancer; IN vitro studies; FLOW cytometry; HERBAL medicine; IN vivo studies; CANCER chemotherapy; IMMUNOHISTOCHEMISTRY; WESTERN immunoblotting; ANTINEOPLASTIC agents; MAGNETIC resonance imaging; MICRORNA; APOPTOSIS; CONNEXINS; CELLULAR signal transduction; TREATMENT effectiveness; RADIONUCLIDE imaging; COMPARATIVE studies; CISPLATIN; DRUG interactions; DESCRIPTIVE statistics; CHI-squared test; KAPLAN-Meier estimator; CELL proliferation; SURVIVAL analysis (Biometry); RESEARCH funding; MITOGEN-activated protein kinases; COMPUTED tomography; DATA analysis software; RECEIVER operating characteristic curves; POLYMERASE chain reaction; CHINESE medicine; DRUG resistance in cancer cells; LONGITUDINAL method; PHARMACODYNAMICS
- Publication
American Journal of Chinese Medicine, 2022, Vol 50, Issue 7, p1963
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X22500847