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Abstract：
Background: 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. Methods: 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. Results: 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. Conclusion: We demonstrate that ZQD can effectively reduce cell proliferation and tumor growth by inhibiting the activation of IL-6/STAT3 signaling pathway.
摘要：
研究背景:前列腺癌是男性最常见的恶性肿瘤,占全球五大癌症发病率之一。然而,晚期前列腺癌（APC）尚无有效的药物治疗方法。在这里，目的探讨周氏芪灵汤(ZQD)的作用机制,中药复方，抑制前列腺癌细胞增殖和肿瘤生长。方法:测定PC3和DU145细胞的IC50。在白细胞介素(IL)6刺激后使用MTT测定法测定细胞活力。使用集落形成测定评价细胞增殖能力。使用qRT-PCR和Westernblot在PC3和DU145细胞以及异种移植肿瘤组织中分析IL-6/信号转导子和转录激活子3（STAT3）信号通路。结果:发现ZQD显著抑制IL-6诱导的PC3和DU145细胞的细胞活力和增殖。此外，ZQD显著降低IL-6、IL-1β、IL-6刺激的STAT3、Bcl2和CyclinD1。在PC3和DU145细胞中,通过40mg/mL的ZQD处理,p-STAT3、Bcl2和CyclinD1的蛋白质水平均降低。此外,在异种移植肿瘤组织中，肿瘤体积,ZQD治疗可显著降低体重和增殖。此外,体内ZQD处理可显著抑制IL-6和pSTAT3的mRNA和蛋白水平。结论: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。
