Arteannuin B Enhances the Effectiveness of Cisplatin in Non-Small Cell Lung Cancer by Regulating Connexin 43 and MAPK Pathway
- Am J Chin Med. 2022;50(7):1963-1992. doi: 10.1142/S0192415X22500847.
- 1. Department of Pharmacology, College of Pharmacy, P. R. China.
- 2. Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, P. R. China.
- 3. Department of General Surgery, Fourth Affiliated Hospital of Anhui Medical University, Hefei 230002, P. R. China.
- 4. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
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[Formula: see text] 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.