Guizhi Fuling Wan, a Traditional Chinese Herbal Formula, Sensitizes Cisplatin-Resistant Human Ovarian Cancer Cells through Inactivation of the PI3K/AKT/mTOR Pathway.
The aim of the study was to explore the possible mechanisms that Guizhi Fuling Wan (GFW) enhances the sensitivity of the SKOV3/DDP ovarian cancer cells and the resistant xenograft tumours to cisplatin. Rat medicated sera containing GFW were prepared by administering GFW to rats, and the primary bioactive constituents of the sera were gallic acid, paeonol, and paeoniflorin analysed by HPLC/QqQ MS. Cell counting kit-8 analysis was shown that coincubation of the sera with cisplatin/paclitaxel enhanced significantly the cytotoxic effect of cisplatin or paclitaxel in SKOV3/DDP cells. The presence of the rat medicated sera containing GFW resulted in an increase in rhodamine 123 accumulation by flow cytometric assays and a decrease in the protein levels of P-gp, phosphorylation of AKT at Ser473, and mTOR in a dose-dependent manner in SKOV3/DDP cells by western blot analysis, but the sera had no effect on the protein levels of PI3K p110α and total AKT. The low dose of GFW enhanced the anticancer efficacy of cisplatin and paclitaxel treatment in resistant SKOV3/DDP xenograft tumours. GFW could sensitize cisplatin-resistant SKOV3/DDP cells by inhibiting the protein level and function of P-gp, which may be medicated through inactivation of the PI3K/AKT/mTOR pathway.
Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Changjiang Road, Nanyang 473004, China.
Li
0000-0002-4486-0534
L
Han
Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Changjiang Road, Nanyang 473004, China.
Xiaojuan
X
Guo
Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Changjiang Road, Nanyang 473004, China.
Hua
H
Bian
Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Changjiang Road, Nanyang 473004, China.
Lei
L
Yang
College of Pharmaceutical Science, Soochow University, 199 Ren-ai Road, Suzhou 215123, China.
Zhong
Z
Chen
Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Changjiang Road, Nanyang 473004, China.
Wenhua
W
Zang
Affiliated Cancer Hospital, Zhengzhou University, Dongming Road 127, Zhengzhou 450008, China.
Jingke
J
Yang