Docetaxel suppressed cell proliferation through Smad3/HIF-1 alpha-mediated glycolysis in prostate cancer cells

Peng, Junming1,2; He, Zhijun3; Yuan, Yeqing1,2,4; Xie, Jing1,2; Zhou, Yu1,2; Guo, Baochun4,5,6,7,8; Guo, Jinan1,2,4,9

2022-12-19

10.1186/s12964-022-00950-z

CELL COMMUNICATION AND SIGNALING   Impact Factor & Quartile

1478-811X

Background:Tumor glycolysis is a critical event for tumor progression. Docetaxel is widely used as a first-line drug for chemotherapy and shown to have a survival advantage. However, the role of docetaxel in tumor glycolysis remained poorly understood. Methods:The effect of Docetaxel in tumor glycolysis and proliferation were performed by CCK-8, Western blotting, real-time PCR, glucose, and lactate detection and IHC. ChIP and luciferase assay were used to analyze the mechanism of Docetaxel on Smad3-mediated HIF-1 alpha transactivity. Results:In this study, we showed that docetaxel treatment led to a significant inhibition of cell proliferation in prostate cancer cells through PFKP-mediated glycolysis. Addition of lactate, a production of glycolysis, could reverse the inhibitory effect of docetaxel on cell proliferation. Further analysis has demonstrated that phosphorylation of Smad3 (Ser213) was drastically decreased in response to docetaxel stimulation, leading to reduce Smad3 nuclear translocation. Luciferase and Chromatin immunoprecipitation (ChIP) analysis revealed that docetaxel treatment inhibited the binding of Smad3 to the promoter of the HIF-1 alpha gene, suppressing transcriptional activation of HIF-1 alpha. Moreover, ectopic expression of Smad3 in prostate cancer cells could overcome the decreased HIF-1 alpha expression and its target gene PFKP caused by docetaxel treatment. Most importantly, endogenous Smad3 regulated and interacted with HIF-1 alpha, and this interaction was destroyed in response to docetaxel treatment. What's more, both HIF-1 alpha and PFKP expression were significantly reduced in prostate cancer received docetaxel treatment in vivo. Conclusion:These findings extended the essential role of docetaxel and revealed that docetaxel inhibited cell proliferation by targeting Smad3/HIF-1 alpha signaling-mediated tumor Warburg in prostate cancer cells.

Docetaxel Tumor glycolysis Smad3 Cell proliferation Prostate cancer

SCI

English

First ; Corresponding

The Science and Technology Foundation of Shenzhen["81571427","81600620","81702082"] ; The Shenzhen Urology Minimally Invasive Engineering Center[JCYJ20170307095620828] ; [GCZX2015043016165448]

Cell Biology

Cell Biology

WOS:000901446000002

BMC

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Urol, Affiliated Hosp 1, Shenzhen 518055, Guangdong, Peoples R China
2.Jinan Univ, Clin Med Coll 2, Shenzhen Urol Minimally Invas Engn Ctr, Shenzhen 518055, Guangdong, Peoples R China
3.Zhuhai Ctr Maternal & Child Hlth Care, Dept Pharm, Zhuhai 519000, Peoples R China
4.Shenzhen Publ Serv Platform Tumor Precis Med & Mol, Shenzhen, Peoples R China
5.Jinan Univ, Shenzhen Peoples Hosp The Clin Med Coll 2, Shenzhen Key Lab Kidney Dis ZDSYS201504301616234, Shenzhen 518055, Guangdong, Peoples R China
6.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518055, Guangdong, Peoples R China
7.Jinan Univ, Shenzhen Peoples Hosp The Clin Med Coll 2, Dept Nephrol, Shenzhen 518020, Guangdong, Peoples R China
8.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
9.Jinan Univ, Shenzhen Peoples Hosp, Clin Coll 2, Dept Urol, Shenzhen 518000, Peoples R China

Peng, Junming,He, Zhijun,Yuan, Yeqing,et al. Docetaxel suppressed cell proliferation through Smad3/HIF-1 alpha-mediated glycolysis in prostate cancer cells[J]. CELL COMMUNICATION AND SIGNALING,2022,20(1).

Peng, Junming.,He, Zhijun.,Yuan, Yeqing.,Xie, Jing.,Zhou, Yu.,...&Guo, Jinan.(2022).Docetaxel suppressed cell proliferation through Smad3/HIF-1 alpha-mediated glycolysis in prostate cancer cells.CELL COMMUNICATION AND SIGNALING,20(1).

Peng, Junming,et al."Docetaxel suppressed cell proliferation through Smad3/HIF-1 alpha-mediated glycolysis in prostate cancer cells".CELL COMMUNICATION AND SIGNALING 20.1(2022).