Icariin-Curcumol promotes docetaxel sensitivity in prostate cancer through modulation of the PI3K-Akt signaling pathway and the Warburg effect

Cancer Cell International

Research

Congxu Zhu¹  Wen Sheng¹  Bonan Li¹  Tiansong Sun¹  Shida Kuang²  Jin Ding³  Wenjing Xu⁴  Yingqiu Li⁵  Juan Liu⁶  Lemei Zhu⁶ 

[1] Andrology Laboratory, Hunan University of Chinese Medicine, 410208, Changsha, China;School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, 410208, Changsha, China;Andrology Laboratory, Hunan University of Chinese Medicine, 410208, Changsha, China;School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, 410208, Changsha, China;Department of Andrology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, 518133, Shenzhen, China;Department of Dermatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, 410021, Changsha, China;Medical School, Hunan University of Chinese Medicine, 410208, Changsha, China;School of Public Health, Changsha Medical University, 410219, Changsha, China;Academician Workstation, Changsha Medical University, 410219, Changsha, China;

关键词: Prostate cancer;    Docetaxel;    PI3K-Akt signaling pathway;    Warburg effect;    Icariin;    Curcumol;   

DOI  :  10.1186/s12935-023-03042-1

 received in 2023-04-14, accepted in 2023-08-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDocetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms.MethodsRegulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity.ResultsAkt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX.ConclusionOur data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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