论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
Authors Ruan Z, Yang X, Cheng W
Received 17 July 2018
Accepted for publication 21 November 2018
Published 28 December 2018 Volume 2019:11 Pages 389—399
DOI https://doi.org/10.2147/CMAR.S180418
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Professor Nakshatri
Background: Although
surgery, chemotherapy, and radiotherapy eliminate clinically apparent ovarian
tumor, the 5-year survival rate is no more than 45%. Cancer stem cells (CSCs)
have been identified for precaution of tumor metastasis and recurrence in many
kinds of cancers including ovarian cancer.
Aim: This
study aims to explore the function of OCT4, a CSC marker, in ovarian cancer
progression and to investigate its underlying mechanism.
Materials and methods: By
Hoechst side population (SP) technique, CSC-like SP cells from human ovarian
cancer SKOV3 and A2780 cells were isolated and used for this study. shRNA and
lentivirus targeting human OCT4 gene were used to knock down OCT4 in SP
cells and upregulate OCT4 in non-SP (NSP) cells stably. Peficitinib was used to
inhibit JAK/STAT signaling. Cell counting kit-8, flow cytometry, and in vivo
xenograft model were used to evaluate the effects of OCT4/JAK/STAT on the
viability, drug resistance, apoptosis, cycle, and tumorigenesis of the SP
cells. Immunofluorescence staining was used to detect the location of
STAT6.
Results: Results
showed that OCT4 was upregulated in the SP of SKOV3 and A2780 cells when
compared with the NSP cells. Downregulation of OCT4 inhibited SP cell
viability, tumorigenesis, and reduced cell drug resistance and induced a G2/M
phase arrest, while upregulation of OCT4 conferred NSP cell malignant features.
Besides, OCT4 upregulation in NSP cells increased the phosphorylated levels of
proteins in JAK and STAT families, especially in JAK1 and STAT6. Furthermore,
the roles of apoptosis inhibition and viability, invasion, and tumorigenesis
promotions induced by OCT4 in NSP cells were all abolished when adding peficitinib.
Conclusion: Our study
demonstrated that OCT4 accelerated ovarian cancer progression through
activating JAK/STAT signaling pathway.
Keywords: OCT4,
JAK/STAT signaling, ovarian cancer, side population