You Xujun, Wu Yongrong, Li Qixin, Sheng Wen, Zhou Qing, Fu Wei
Graduate School of Hunan University of Chinese Medicine, Changsha, China.
Department of Andrology, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China.
Front Pharmacol. 2022 Jun 29;13:895696. doi: 10.3389/fphar.2022.895696. eCollection 2022.
Prostate cancer (PCa) is an epithelial malignancy of the prostate that currently lacks effective treatment. Traditional Chinese medicine (TCM) can play an anticancer role through regulating the immune system, anti-tumor angiogenesis, regulating tumor cell apoptosis, autophagy dysfunction, and other mechanisms. This study attempted to explore the active ingredients and potential mechanism of action of the Astragalus-Scorpion (A-S) drug pair in PCa, in order to provide new insights into the treatment of PCa. Network pharmacology was used to analyze the A-S drug pair and PCa targets. Bioinformatics analysis was used to analyze the LncRNAs with significant differences in PCa. The expression of LC3 protein was detected by immunofluorescence. CCK8 was used to detect cell proliferation. The expressions of GDPD4-2, AC144450.1, LINC01513, AC004009.2, AL096869.1, AP005210.1, and BX119924.1 were detected by RT-qPCR. The expression of the PI3K/AKT/mTOR pathway and autophagy-related proteins were detected by western blot. LC-MS/MS was used to identify the active components of Astragalus and Scorpion. A-S drug pair and PCa have a total of 163 targets, which were mainly related to the prostate cancer and PI3K/AKT pathways. A-S drug pair inhibited the formation of PCa, promoted the expression of LC3Ⅱ and Beclin1 proteins, and inhibited the expression of P62 and PI3K-AKT pathway proteins in PCa mice. Astragaloside IV and polypeptide extract from scorpion venom (PESV) were identified as the main active components of the A-S drug pair. GDPD4-2 was involved in the treatment of PCa by Astragaloside IV-PESV. Silencing GDPD4-2 reversed the therapeutic effects of Astragaloside IV-PESV by regulating the PI3K/AKT/mTOR pathway. Astragaloside IV-PESV is the main active components of A-S drug pair treated PCa by regulating the GDPD4-2/PI3K-AKT/mTOR pathway and autophagy.
前列腺癌（PCa）是一种前列腺上皮恶性肿瘤，目前缺乏有效的治疗方法。中药可以通过调节免疫系统、抗肿瘤血管生成、调节肿瘤细胞凋亡、自噬功能障碍等机制发挥抗癌作用。本研究试图探索黄芪 - 全蝎（A - S）药对在前列腺癌中的活性成分及潜在作用机制，为前列腺癌的治疗提供新的见解。采用网络药理学分析A - S药对与前列腺癌的靶点。利用生物信息学分析前列腺癌中差异显著的长链非编码RNA（LncRNAs）。通过免疫荧光检测LC3蛋白的表达。使用CCK8检测细胞增殖。通过逆转录 - 定量聚合酶链反应（RT - qPCR）检测GDPD4 - 2、AC144450.1、LINC01513、AC004009.2、AL096869.1、AP005210.1和BX119924.1的表达。通过蛋白质免疫印迹法检测PI3K/AKT/mTOR通路及自噬相关蛋白的表达。采用液相色谱 - 串联质谱（LC - MS/MS）鉴定黄芪和全蝎的活性成分。A - S药对与前列腺癌共有163个靶点，主要与前列腺癌及PI3K/AKT通路相关。A - S药对抑制前列腺癌的形成，促进PCa小鼠中LC3Ⅱ和Beclin1蛋白的表达，并抑制P62和PI3K - AKT通路蛋白的表达。黄芪甲苷IV和蝎毒多肽提取物（PESV）被鉴定为A - S药对的主要活性成分。GDPD4 - 2参与了黄芪甲苷IV - PESV对前列腺癌的治疗。沉默GDPD4 - 2通过调节PI3K/AKT/mTOR通路逆转了黄芪甲苷IV - PESV的治疗效果。黄芪甲苷IV - PESV是A - S药对通过调节GDPD4 - 2/PI3K - AKT/mTOR通路和自噬治疗前列腺癌的主要活性成分。
