Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, 13 Wuhe Road, Qingxiu District, Nanning 530200, China; Institute of Marine Drugs, Guangxi University of Chinese Medicine, 13 Wuhe Road, Qingxiu District, Nanning 530200, China.
Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, 13 Wuhe Road, Qingxiu District, Nanning 530200, China.
Biomed Pharmacother. 2022 Aug;152:113266. doi: 10.1016/j.biopha.2022.113266. Epub 2022 Jun 9.
Prostate cancer is a disease that often occurs in elderly men. Androgen receptor signaling pathway runs through the occurrence and development of prostate cancer. Thereby, targeting androgen receptor is a crucial strategy for the treatment of prostate cancer. α-Terthienyl, which has been used as photosensitive activator and insecticide, is a natural compound rich in marigold. In the present study, we found α- terthienyl could inhibit the cell viability of four prostate cancer cell lines, especially on LNCaP and 22Rv1 cells which endogenously express androgen receptor. Then we proved that it could inhibit the proliferation of prostate cancer cells and induce apoptosis of prostate cancer cells by plate clone formation assay and flow cytometry respectively. Furthermore, we found α-terthienyl could inhibit androgen receptor nuclear translocation, reduce androgen receptor expression, reduce the mRNA and protein expression of androgen receptor target genes (KLK3, TMPRSS2, PCA3) and nuclear proliferation antigen Ki67 and PCNA. In addition, it inhibited the expression and phosphorylation of Akt protein while increasing the expression of tumor suppressor p27. Besides, we constructed a mouse xenograft prostate cancer model and confirmed that α-terthienyl also inhibited the growth of prostate cancer in vivo. In conclusively, α-terthienyl played an anti-prostate cancer role by inhibiting both the expression of androgen receptor and the transduction of its signal pathway, suggesting that it is a promising natural small molecule for the treatment of prostate cancer.
前列腺癌是一种常见于老年男性的疾病。雄激素受体信号通路贯穿于前列腺癌的发生和发展。因此，靶向雄激素受体是治疗前列腺癌的关键策略。α-噻吩，曾作为光敏激活剂和杀虫剂，是一种富含万寿菊的天然化合物。在本研究中，我们发现α-噻吩可以抑制四种前列腺癌细胞系的细胞活力，尤其是对表达内源性雄激素受体的 LNCaP 和 22Rv1 细胞。然后我们通过平板克隆形成实验和流式细胞术分别证明它可以抑制前列腺癌细胞的增殖并诱导前列腺癌细胞凋亡。此外，我们发现α-噻吩可以抑制雄激素受体核易位，降低雄激素受体表达，降低雄激素受体靶基因（KLK3、TMPRSS2、PCA3）和核增殖抗原 Ki67 和 PCNA 的 mRNA 和蛋白表达。此外，它还抑制 Akt 蛋白的表达和磷酸化，同时增加肿瘤抑制因子 p27 的表达。此外，我们构建了小鼠异种移植前列腺癌模型，并证实α-噻吩也能抑制体内前列腺癌的生长。总之，α-噻吩通过抑制雄激素受体的表达及其信号通路的转导发挥抗前列腺癌作用，表明它是一种有前途的治疗前列腺癌的天然小分子。
