Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning 530200, China.
Guangxi Key Laboratory of Applied Fundamental Research of Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China.
Int J Mol Sci. 2023 Sep 25;24(19):14519. doi: 10.3390/ijms241914519.
Docetaxel is a first-line chemotherapy drug used to treat advanced prostate cancer, but patients who have used it often face the challenges of drug resistance and side effects. Kaempferol is a naturally occurring flavonol; our previous studies have confirmed that it has excellent anti-prostate activity. To investigate the anti-prostate cancer effects of docetaxel in combination with kaempferol, we conducted experiments at the cellular and whole-animal level. Plate cloning assays showed that the combination of docetaxel and kaempferol had a synergistic effect in inhibiting the proliferation of prostate cancer cells. The combination of these two compounds was found to induce autophagy in prostate cancer cells via transmission electron microscopy, and changes in the expression of autophagy-related proteins via Western blot assays also confirmed the occurrence of autophagy at the molecular level. We also confirmed the anti-prostate cancer effect of docetaxel in combination with kaempferol in vivo by establishing a mouse xenograft prostate cancer model. Autophagy-related proteins were also examined in mouse tumor tissues and verified the presence of autophagy in mouse tumor tissues. The above cellular and animal data suggest that docetaxel in combination with kaempferol has significant anti-prostate cancer effects and that it works by inducing autophagy in cells.
多西他赛是一种用于治疗晚期前列腺癌的一线化疗药物,但使用过它的患者常常面临耐药性和副作用的挑战。山奈酚是一种天然存在的类黄酮;我们之前的研究已经证实它具有出色的抗前列腺活性。为了研究多西他赛与山奈酚联合治疗前列腺癌的效果,我们在细胞和整体动物水平上进行了实验。平板克隆实验表明,多西他赛和山奈酚联合使用对抑制前列腺癌细胞增殖具有协同作用。通过透射电子显微镜发现,这两种化合物的组合通过诱导自噬来抑制前列腺癌细胞,Western blot 实验检测自噬相关蛋白的表达变化也证实了自噬在分子水平上的发生。我们还通过建立小鼠异种移植前列腺癌模型,在体内证实了多西他赛与山奈酚联合使用的抗前列腺癌效果。在小鼠肿瘤组织中还检查了自噬相关蛋白,并验证了小鼠肿瘤组织中存在自噬。上述细胞和动物数据表明,多西他赛与山奈酚联合具有显著的抗前列腺癌作用,其作用机制是诱导细胞自噬。