Ruan Shanming, Zhang Haizhong, Tian Xinxin, Zhang Zhiqian, Huang Hong, Shi Chao, Liu Wenhong, Jiang Xiawei, Huang Dawei, Tao Fangfang
Department of Medical Oncology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Front Pharmacol. 2020 Feb 28;11:150. doi: 10.3389/fphar.2020.00150. eCollection 2020.
Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. We have previously reported that compound fuling granule (CFG), a traditional Chinese medicinal preparation used to treat ovarian cancer in China for over 20 years, significantly promotes cell cycle arrest, apoptosis, senescence, TGFβ-induced invasion and migration, tumor growth, and distant metastasis in ovarian cancer cells. However, the underlying mechanisms are not clear. In the present study, we found that PHF19 expression in ovarian cancer cells positively correlated with their resistance ability to CFG. In addition, PHF19 overexpression increased the resistance of HEY-T30 and SKOV3 cells to CFG, while knockdown of PHF19 enhanced their sensitivity to CFG. Moreover, CFG significantly inhibited the expression of PHF19 both in mRNA and protein levels in these cells. Gain of function and loss of function experiments further proved that PHF19 is a crucial mediator involved in the ovarian cancer progression, including cell proliferation, invasion, migration, and stemness. Importantly, rescue the expression of PHF19 reverted CFG-induced suppression in ovarian cancer cell growth, EMT and stemness, while PHF19 knockdown accelerated CFG's anti-tumor effect. Overall, our results provide a series of evidence to reveal that PHF19 is critical suppressor for CFG's anti-tumor effect in ovarian cancer.
卵巢癌是全球女性中最常见的妇科恶性肿瘤之一,生存率较低。我们之前报道过,复方茯苓颗粒(CFG)是一种在中国用于治疗卵巢癌超过20年的传统中药制剂,它能显著促进卵巢癌细胞的细胞周期停滞、凋亡、衰老、TGFβ诱导的侵袭和迁移、肿瘤生长以及远处转移。然而,其潜在机制尚不清楚。在本研究中,我们发现卵巢癌细胞中PHF19的表达与其对CFG的耐药能力呈正相关。此外,PHF19过表达增加了HEY-T30和SKOV3细胞对CFG的耐药性,而敲低PHF19则增强了它们对CFG的敏感性。此外,CFG在mRNA和蛋白质水平上均显著抑制这些细胞中PHF19的表达。功能获得和功能丧失实验进一步证明,PHF19是参与卵巢癌进展的关键介质,包括细胞增殖、侵袭、迁移和干性。重要的是,恢复PHF19的表达可逆转CFG诱导的卵巢癌细胞生长、EMT和干性抑制,而敲低PHF19则加速了CFG的抗肿瘤作用。总体而言,我们的结果提供了一系列证据,揭示了PHF19是CFG在卵巢癌中抗肿瘤作用的关键抑制因子。