Docetaxel

Docetaxel is a taxane class of anti-mitotic chemotherapeutic agents with an IC50 of 0.2 µM. It preferentially binds to β-tubulin, suppresses microtubule dynamics, disrupts cell division, and therefore effectively induces apoptosis. Docetaxel has anti-cancer activity[1-3].

Docetaxel(5 uM;24-72h) suppressed PC-3M IE8 cell proliferation and aerobic glycolysis[4]. Docetaxel(50 nM; 12-48 h) inhibited the proliferation while it enhanced the apoptosis of human CD133 expressing HCC stem cells[5]. Docetaxel treatment activates lysosomal function and promotes its fusion with autophagosome[6].

Docetaxel-based(10 mg/kg Docetaxel per injection；i.p; once per week for two consecutive weeks) chemohormonal therapy prompted the intratumoral infiltration of T cells and upregulated the abundance of PD1 and PD-L1, thereby sensitizing mouse tumors to the anti-PD1 blockade in a xenograft mouse model[7-8].

References:
[1]. James ND, Sydes MR, et,al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1163-77. doi: 10.1016/S0140-6736(15)01037-5. Epub 2015 Dec 21. PMID: 26719232; PMCID: PMC4800035.
[2]. Sweeney CJ, Chen YH, et,al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5. PMID: 26244877; PMCID: PMC4562797.
[3]. Buey RM, DÍaz JF, et,al. Interaction of epothilone analogs with the paclitaxel binding site: relationship between binding affinity, microtubule stabilization, and cytotoxicity. Chem Biol. 2004 Feb;11(2):225-36. doi: 10.1016/j.chembiol.2004.01.014. PMID: 15123284.
[4]. Peng J, He Z, et,al. Docetaxel suppressed cell proliferation through Smad3/HIF-1α-mediated glycolysis in prostate cancer cells. Cell Commun Signal. 2022 Dec 19;20(1):194. doi: 10.1186/s12964-022-00950-z. PMID: 36536346; PMCID: PMC9762006.
[5]. Zhang X, Shao J, et,al. Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway. Oncol Rep. 2019 Feb;41(2):1067-1074. doi: 10.3892/or.2018.6891. Epub 2018 Nov 27. PMID: 30483804.
[6]. Zhang J, Wang J, et,al. Docetaxel enhances lysosomal function through TFEB activation. Cell Death Dis. 2018 May 23;9(6):614. doi: 10.1038/s41419-018-0571-4. PMID: 29795139; PMCID: PMC5966422.
[7]. Ma Z, Zhang W, et,al. Docetaxel remodels prostate cancer immune microenvironment and enhances checkpoint inhibitor-based immunotherapy. Theranostics. 2022 Jun 27;12(11):4965-4979. doi: 10.7150/thno.73152. PMID: 35836810; PMCID: PMC9274752.
[8]. Yu Y, Yang FH, et,al. Mesenchymal stem cells desensitize castration-resistant prostate cancer to docetaxel chemotherapy via inducing TGF-beta1-mediated cell autophagy. Cell Biosci. 2021;11(1):7.