PMID- 35527911 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2046-2069 (Electronic) IS - 2046-2069 (Linking) VI - 9 IP - 42 DP - 2019 Aug 2 TI - Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma. PG - 24471-24482 LID - 10.1039/c9ra04701h [doi] AB - Laryngeal squamous cell carcinoma (LSCC) is the most common head and neck cancer. Astragali radix extracts play crucial roles in the regulation of cancer progression. However, the role of Astragali radix extracts in LSCC and the related mechanisms remains unclear. Here, we evaluated the inhibitory effects of the combined use of Astragali radix total flavonoid (TFA) and cisplatin (CDDP) on an LSCC mouse model by pharmacodynamics. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to define the prototype of TFA in vivo. The potential drug targets were identified through the integrative analysis of LSCC microarrays, RNA sequencing data and the main bioactive component of TFA. Furthermore, a protein-protein interaction network, compound-target network and target-pathway network were constructed based on the prototype and potential drug targets to identify the main targets and pathways. Animal experiments showed that TFA has significant synergistic antitumor activity with cisplatin and attenuates the nephrotoxicity caused by CDDP chemotherapy, improving the survival of LSCC-bearing mice. Using UPLC-MS/MS, we identified 8 constituents of TFA in experimental mice serum: formononetin, ononin, calycosin, calycosin-7-O-beta-D-glucoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, 7,2'-dihydroxy-3',4'-dimethoxyisoflavaneglucoside, 3-hydroxy-9,10-dimethoxypterocarpan and 9,10-dimethoxyptercarpan-3-O-beta-d-glucoside. Integrative analysis predicted 19 target genes for TFA constituents, and the target genes were mainly involved in the EGFR-related cancer signaling, metabolism and oxidative stress. Collectively, these findings highlight the role of TFA in the regulation of LSCC and provide potential targets for a high-efficiency and low-toxicity therapeutic strategy of LSCC. CI - This journal is (c) The Royal Society of Chemistry. FAU - Cui, Jiajia AU - Cui J AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - Zheng, Xiwang AU - Zheng X AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - Yang, Dongli AU - Yang D AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China. FAU - Hu, Yinghuan AU - Hu Y AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - An, Changming AU - An C AD - Department of Head and Neck Surgery, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing 100021 China. FAU - Bo, Yunfeng AU - Bo Y AD - Department of Pathology, Shanxi Cancer Hospital, Shanxi Medical University Taiyuan 030001 Shanxi China. FAU - Li, Huizheng AU - Li H AD - Department of Otolaryngology Head & Neck Surgery, Dalian Municipal Friendship Hospital Dalian 116001 Liaoning China. FAU - Zhang, Yuliang AU - Zhang Y AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - Niu, Min AU - Niu M AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - Xue, Xuting AU - Xue X AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - Lu, Yan AU - Lu Y AD - Department of Otolaryngology Head & Neck Surgery, The First Hospital, Jinzhou Medical University Jinzhou 121001 Liaoning China. FAU - Tang, Yemei AU - Tang Y AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China. FAU - Yin, Hongyu AU - Yin H AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China. FAU - Li, Zhenyu AU - Li Z AUID- ORCID: 0000-0003-0655-6942 AD - Modern Research Center for Traditional Chinese Medicine, Shanxi University Taiyuan 030001 Shanxi China lizhenyu@sxu.edu.cn. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - Gao, Wei AU - Gao W AUID- ORCID: 0000-0001-7836-2851 AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. FAU - Wu, Yongyan AU - Wu Y AUID- ORCID: 0000-0003-1669-3860 AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China wuyongyan@sxent.org gaoweisxent@sxent.org. AD - Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province Taiyuan 030001 Shanxi China. LA - eng PT - Journal Article DEP - 20190807 PL - England TA - RSC Adv JT - RSC advances JID - 101581657 PMC - PMC9069756 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2019/08/07 00:00 MHDA- 2019/08/07 00:01 PMCR- 2019/08/07 CRDT- 2022/05/09 03:48 PHST- 2019/06/23 00:00 [received] PHST- 2019/07/19 00:00 [accepted] PHST- 2022/05/09 03:48 [entrez] PHST- 2019/08/07 00:00 [pubmed] PHST- 2019/08/07 00:01 [medline] PHST- 2019/08/07 00:00 [pmc-release] AID - c9ra04701h [pii] AID - 10.1039/c9ra04701h [doi] PST - epublish SO - RSC Adv. 2019 Aug 7;9(42):24471-24482. doi: 10.1039/c9ra04701h. eCollection 2019 Aug 2.