Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung 110122, Taiwan.
Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 110122, Taiwan.
Int J Mol Sci. 2019 Sep 8;20(18):4418. doi: 10.3390/ijms20184418.
Resistance to the current therapies is the main clinical challenge in the treatment of lethal metastatic prostate cancer (mPCa). Developing novel therapeutic approaches with effective regimes and minimal side effects for this fatal disease remain a priority in prostate cancer study. In the present study, we demonstrated that a traditional Chinese medicine, quality-assured ethanol extract (GTEE), significantly suppressed cell growth and metastatic capability and caused cell cycle arrest through decreasing expression of cyclins in mPCa cells, PC-3 and DU145 cells. GTEE also induced caspase-dependent apoptosis in mPCa cells. We further showed the potent therapeutic efficacy of GTEE by inhibiting subcutaneous PC-3 tumor growth in a xenograft model. The in vitro and in vivo efficacies on mPCa cells were due to blockade of the PI3K/Akt and MAPK/ERK signaling pathways associated with cancer cell growth, survival and apoptosis. These preclinical data provide the molecular basis for a new potential therapeutic approach toward the treatment of lethal prostate cancer progression.
目前治疗致命转移性前列腺癌(mPCa)的主要临床挑战是对现有疗法的耐药性。对于这种致命疾病,开发具有有效治疗方案和最小副作用的新型治疗方法仍然是前列腺癌研究的重点。在本研究中,我们证明了一种中药,质量保证的乙醇提取物(GTEE),通过降低 mPCa 细胞、PC-3 和 DU145 细胞中环蛋白的表达,显著抑制细胞生长和转移能力,并导致细胞周期停滞。GTEE 还诱导 mPCa 细胞中 caspase 依赖性细胞凋亡。我们通过抑制异种移植模型中皮下 PC-3 肿瘤生长进一步证明了 GTEE 的强大治疗功效。对 mPCa 细胞的体外和体内功效归因于阻断与癌细胞生长、存活和凋亡相关的 PI3K/Akt 和 MAPK/ERK 信号通路。这些临床前数据为治疗致命性前列腺癌进展的新的潜在治疗方法提供了分子基础。