Article ; Online: Jie Geng Tang reverses cisplatin resistance through the Nrf2 pathway in lung cancer.
The Journal of pharmacy and pharmacology
2023 Volume 75, Issue 6, Page(s) 784–805
Abstract: Objectives: Jie Geng Tang (JGT) is an ancient traditional Chinese herbal decoction that exhibits ...
| Abstract | Objectives: Jie Geng Tang (JGT) is an ancient traditional Chinese herbal decoction that exhibits various pharmacological activities, however, is poorly understood in the sensitivity of lung cancer to chemotherapy. Here, we explored the effect of JGT on sensitizing cisplatin (DDP)-resistant A549 cells (A549/DDP). Methods: Cell viability was assessed using cell counting kit-8 assay. Flow cytometry was applied to detected cell apoptosis, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. Western blotting and qRT-PCR were performed to determine protein and mRNA levels. Key findings: The results demonstrated that DDP co-treatment with JGT significantly increased the cytotoxicity of A549/DDP cells and exhibited efficacy in suppressing the migration and proliferation. The rate of apoptosis was increased by co-treatment with DDP and JGT, along with a higher rate of Bax/Bcl-2, and increased loss of MMP. Furthermore, the combination promoted ROS accumulation and increased γ-H2AX levels. Moreover, Nrf2 levels were suppressed in a dose- and time-dependent manner, Nrf2 stability was reduced following treatment with JGT. Notably, the combination induced inhibition of the Nrf2/ARE pathway at the mRNA and protein levels. Conclusions: Collectively, these results indicate that co-treatment with JGT and DDP can be considered a combinational approach to treating DDP resistance. |
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| MeSH term(s) | Humans ; Cisplatin/pharmacology ; NF-E2-Related Factor 2/metabolism ; Reactive Oxygen Species/metabolism ; Drug Resistance, Neoplasm ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Apoptosis ; Cell Proliferation ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor |
| Chemical Substances | Cisplatin (Q20Q21Q62J) ; NF-E2-Related Factor 2 ; Reactive Oxygen Species ; Antineoplastic Agents |
| Language | English |
| Publishing date | 2023-03-28 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 3107-0 |
| ISSN | 2042-7158 ; 0022-3573 ; 0373-1022 |
| ISSN (online) | 2042-7158 |
| ISSN | 0022-3573 ; 0373-1022 |
| DOI | 10.1093/jpp/rgad018 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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