Cao Hongwen, Feng Yigeng, Sun Peng, Chen Lei, Wang Dan, Gao Renjie
Surgical Department I (Urology Department), LONGHUA Hospital Shanghai University of Traditional Chinese Medicine, No. 725 Wanping Road South, Xuhui District, Shanghai 200032, China.
J Cancer. 2023 Jul 16;14(12):2246-2254. doi: 10.7150/jca.84943. eCollection 2023.
Prostate cancer is the most common malignant tumor in men, accounting for one of the top five cancer incidences worldwide. However, there is no effective pharmacological treatment for advanced prostate cancer (APC). Herein, we aim to investigate the mechanism of Zhoushi Qiling decoction (ZQD), a traditional Chinese medicine compound, in inhibiting prostate cancer cells proliferation and tumor growth. IC50 was determined in PC3 and DU145 cells. Cell viability was determined using MTT assay after interleukin (IL) 6 stimulation. Cell proliferation ability was evaluated using colony formation assay. IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway was analyzed using qRT-PCR and Western blot in PC3 and DU145 cells and xenograft tumor tissues. It was found that ZQD significantly inhibited Il-6-induced cell viability and proliferation in PC3 and DU145 cells. Moreover, ZQD significantly reduced mRNA levels of IL-6, IL-1β, STAT3, Bcl2, and CyclinD1, stimulated by IL-6. The protein levels of p-STAT3, Bcl2 and CyclinD1 were reduced by ZQD treatment at 40 mg/mL both in PC3 and DU145 cells. Additionally, in xenograft tumor tissues, tumor volume, weight and proliferation were significantly reduced by ZQD treatment. In addition, the mRNA and protein levels of IL-6 and pSTAT3 were significantly inhibited by ZQD treatment in vivo. We demonstrate that ZQD can effectively reduce cell proliferation and tumor growth by inhibiting the activation of IL-6/STAT3 signaling pathway.
前列腺癌是男性最常见的恶性肿瘤,占全球癌症发病率前五之一。然而,对于晚期前列腺癌(APC)尚无有效的药物治疗方法。在此,我们旨在研究中药复方周氏启灵汤(ZQD)抑制前列腺癌细胞增殖和肿瘤生长的机制。在PC3和DU145细胞中测定IC50。在白细胞介素(IL)-6刺激后,使用MTT法测定细胞活力。使用集落形成试验评估细胞增殖能力。在PC3和DU145细胞以及异种移植肿瘤组织中,使用qRT-PCR和蛋白质印迹法分析IL-6/信号转导和转录激活因子3(STAT3)信号通路。结果发现,ZQD显著抑制IL-6诱导的PC3和DU145细胞的活力和增殖。此外,ZQD显著降低了IL-6刺激的IL-6、IL-1β、STAT3、Bcl2和细胞周期蛋白D1的mRNA水平。在PC3和DU145细胞中,40mg/mL的ZQD处理降低了p-STAT3、Bcl2和细胞周期蛋白D1的蛋白质水平。此外,在异种移植肿瘤组织中,ZQD处理显著降低了肿瘤体积、重量和增殖。另外,在体内,ZQD处理显著抑制了IL-6和pSTAT3的mRNA和蛋白质水平。我们证明,ZQD可通过抑制IL-6/STAT3信号通路的激活有效降低细胞增殖和肿瘤生长。