Oroxylin a reverses hypoxia-induced cisplatin resistance through inhibiting hif-1α mediated xpc transcription

ABSTRACT Hypoxia is a key concern during the treatment of non-small cell lung cancer (NSCLC), and hypoxia-inducible factor 1 alpha (HIF-1α) has been associated with increased tumor

resistance to therapeutic modalities such as cisplatin. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism that accounts for cisplatin resistance. In

the present study, we suggest a novel strategy to improve the treatment of NSCLC and overcome the hypoxia-induced cisplatin resistance by cotreatment with Oroxylin A, one of the main

bioactive flavonoids of _Scutellariae radix_. Based on the preliminary screening, we found that xeroderma pigmentosum group C (XPC), an important DNA damage recognition protein involved in

NER, dramatically increased in hypoxic condition and contributed to hypoxia-induced cisplatin resistance. Further data suggested that Oroxylin A significantly reversed the hypoxia-induced

cisplatin resistance through directly binding to HIF-1α bHLH-PAS domain and blocking its binding to HRE3 transcription factor binding sites on _XPC_ promoter which is important to

hypoxia-induced _XPC_ transcription. Taken together, our findings not only demonstrate a crucial role of XPC dependent NER in hypoxia-induced cisplatin resistance, but also suggest a

previously unrecognized tumor suppressive mechanism of Oroxylin A in NSCLC which through sensitization of cisplatin-mediated growth inhibition and apoptosis under hypoxia. Access through

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BEING VIEWED BY OTHERS CEPHALOMANNINE INHIBITS HYPOXIA-INDUCED CELLULAR FUNCTION VIA THE SUPPRESSION OF APEX1/HIF-1Α INTERACTION IN LUNG CANCER Article Open access 14 May 2021 INFLUENCES OF

AQUA-(2-FORMYLBENZOATO) TRIPHENYLTIN(IV) ON REGRESSION OF HYPOXIC SOLID TUMOR THROUGH MITOCHONDRIAL MEDIATED PATHWAY BY INHIBITING HIF-1 ALPHA Article Open access 12 February 2025 NPAS2

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Scholar  Download references ACKNOWLEDGEMENTS We are grateful to Dr. Feihong Chen (Southeast University at Nanjing, China) for kindly providing CDDP-resistant A549/CDDP cells and Dr. Zhaoqiu

Wu (China Pharmaceutical university, Nanjing, China) for kindly providing pGEX-6P-1 plasmids. FUNDING This work was supported by the China Postdoctoral Science Foundation Grant

(2019M652035); the General Program of National Natural Science Foundation of China (81772911, 81974425, and 81903648); the Natural Science Foundation of Jiangsu Province (BK20170744); the

Six Talent Peaks Project in Jiangsu Province (SWYY-095). AUTHOR INFORMATION Author notes * These authors contributed equally: Yunyao Liu, Xiaoping Wang AUTHORS AND AFFILIATIONS * State Key

Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China Yunyao Liu, Xiaoping Wang, Wenshu Li, Yujiao Xu, Yating Zhuo,

 Yuan He, Qinglong Guo & Lei Qiang * Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China Mengyuan Li 

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CITE THIS ARTICLE Liu, Y., Wang, X., Li, W. _et al._ Oroxylin A reverses hypoxia-induced cisplatin resistance through inhibiting HIF-1α mediated XPC transcription. _Oncogene_ 39, 6893–6905

(2020). https://doi.org/10.1038/s41388-020-01474-x Download citation * Received: 13 January 2020 * Revised: 04 September 2020 * Accepted: 15 September 2020 * Published: 25 September 2020 *

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