PHD Finger Protein 19 Enhances the Resistance of Ovarian Cancer Cells to Compound Fuling Granule by Protecting Cell Growth, Invasion, Migration, and Stemness

PHD指蛋白19通过保护细胞生长、侵袭、迁移和干细胞特性增强卵巢癌细胞对复方茯苓颗粒的抵抗力

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作者:Shanming Ruan, Haizhong Zhang, Xinxin Tian, Zhiqian Zhang, Hong Huang, Chao Shi, Wenhong Liu, Xiawei Jiang, Dawei Huang, Fangfang Tao

Abstract

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.

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