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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1405521
Synergistic antitumor activity of baicalein combined with almonertinib in almonertinibresistant non-small cell lung cancer cells through ROS-mediated PI3K/Akt pathway
Provisionally accepted
Teng Chen
1
Pei Zhang
1,2*
Xiao-Fan Cong
1*
Yuan-Yuan Wang
1*
Shuo Li
1*
Hao Wang
1*
Su-Rong Zhao
1,2*
Xiao-Jin Sun
1,2*- 1 School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, China
- 2 Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui Province, China
Almonertinib, an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), exhibits high selectivity to EGFR-sensitizing and T790M resistance mutations. Nevertheless, almonertinib resistance is a major obstacle in clinical use. Baicalein, possessing antitumor property, but the mechanism of its anti-tumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains yet unelucidated. In the current study, we intended to evaluate the effect of baicalein and/or almonertinib on proliferation, apoptosis, and associated pathways in almonertinib-resistant NSCLC HCC827/AR and H1975/AR cells. The findings presented that baicalein or almonertinib repressed cell viability of HCC827/AR and H1975/AR cells concentrationdependently. The combined application of the two drugs dramatically attenuated the cell proliferation, triggered apoptosis, caused the cleavage of Caspase-3, PARP, and Caspase-9, and significantly inhibited the tumor growth in nude mice. Furthermore, based upon the findings of network pharmacology study, it was found that baicalein combined with almonertinib led to a massive accumulation of ROS, and pre-incubation with N-acetyl-L-cysteine (ROS remover) prevented the proliferation inhibition and apoptosis induction by combination treatment, and partially recovered the decline of p-Akt andp-PI3K, highlighting the crucial role of ROS in apoptosis and PI3K/Akt pathway. In conclusion, these findings implied that baicalein combined with almonertinib improved antitumor activity in almonertinib-resistant NSCLC through ROS-mediated PI3K/Akt pathway.
Keywords: Baicalein, Almonertinib, resistant, Non-small cell lung cancer, Apoptosis, Reactive Oxygen Species, PI3K/Akt signaling pathway
Received: 23 Mar 2024; Accepted: 01 Jul 2024.
Copyright: © 2024 Chen, Zhang, Cong, Wang, Li, Wang, Zhao and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Pei Zhang, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui Province, China
Xiao-Fan Cong, School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, China
Yuan-Yuan Wang, School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, China
Shuo Li, School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, China
Hao Wang, School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, China
Su-Rong Zhao, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui Province, China
Xiao-Jin Sun, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui Province, China
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