Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Ovarian cancer is a deadly gynecological malignancy with resistance to cisplatin a major clinical problem. We evaluated a role of long non-coding (lnc) RNA HOTTIP (HOXA transcript at the distal tip) in the cisplatin resistance of ovarian cancer cells, using paired cisplatin sensitive and resistant A2780 cells along with the SK-OV-3 cells. HOTTIP was significantly elevated in cisplatin resistant cells and its silencing reversed the cisplatin resistance of resistant cells. HOTTIP was found to sponge miR-205 and therefore HOTTIP silenced cells had higher levels of miR-205. Downregulation of miR-205 could attenuate HOTTIP-silencing effects whereas miR-205 upregulation in resistant cells was found to re-sensitize cells to cisplatin. HOTTIP silencing also led to reduced NF-κB activation, clonogenic potential and the reduced expression of stem cell markers SOX2, OCT4, and NANOG, an effect that could be attenuated by miR-205. Finally, ZEB2 was identified as the gene target of miR-205, thus completing the elucidation of HOTTIP-miR-205-ZEB2 as the novel axis which is functionally involved in the determination of cisplatin resistance in ovarian cancer cells.

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Proteins Associated with Cisplatin Resistance in Ovarian Cancer Cells Identified by Quantitative Proteomic Technology and Integrated with mRNA Expression Levels

Molecular & Cellular Proteomics ◽

10.1074/mcp.m500140-mcp200 ◽

2005 ◽

Vol 5 (3) ◽

pp. 433-443 ◽

Cited By ~ 95

Author(s):

Jennifer J. Stewart ◽

James T. White ◽

Xiaowei Yan ◽

Steven Collins ◽

Charles W. Drescher ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Cisplatin Resistance ◽

Ovarian Cancer Cells ◽

Expression Levels ◽

Proteomic Technology ◽

Mrna Expression Levels

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Targeting and neutralizing human epididymis protein 4 by novel nanobodies to suppress ovarian cancer cells and attenuate cisplatin resistance

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2022.01.015 ◽

2022 ◽

Author(s):

Jianli Yu ◽

Yang Guo ◽

Yi Gu ◽

Fei Li ◽

Haipeng Song ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cisplatin Resistance ◽

Ovarian Cancer Cells ◽

Human Epididymis Protein 4 ◽

Human Epididymis

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Identification of reproducible low mass SELDI protein profiles specific to cisplatin resistance in human ovarian cancer cells

Oncology Reports ◽

10.3892/or.14.5.1323 ◽

2005 ◽

Cited By ~ 1

Author(s):

Richard Britten ◽

Carrie Hardy ◽

Antonia Vlahou ◽

Betsy Gregory ◽

P. Giri ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cisplatin Resistance ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Protein Profiles ◽

Low Mass

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Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

Cellular Physiology and Biochemistry ◽

10.1159/000447818 ◽

2016 ◽

Vol 39 (3) ◽

pp. 1098-1110 ◽

Cited By ~ 11

Author(s):

Chanjuan Li ◽

Hongjuan Ding ◽

Jing Tian ◽

Lili Wu ◽

Yun Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Line ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cell Line ◽

Cancer Cell Line ◽

Ovarian Cancer Cells ◽

Skov3 Cell ◽

Mesenchymal Transition ◽

Forkhead Box

Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3β signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. Conclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

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