scholarly journals Resensitization of cisplatin resistance ovarian cancer cells to cisplatin through pretreatment with low‐dose fraction radiation

2019 ◽  
Vol 8 (5) ◽  
pp. 2442-2448
Author(s):  
Lili Zhao ◽  
Shihai Liu ◽  
Donghai Liang ◽  
Tao Jiang ◽  
Xiaoyan Yan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Low Dose ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cells ◽  
Dose Fraction

scholarly journals HOTTIP-miR-205-ZEB2 Axis Confers Cisplatin Resistance to Ovarian Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Jie Dong ◽  
Wei Feng ◽  
Yan Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Clinical Problem ◽  
Ovarian Cancer Cells ◽  
Stem Cell Markers ◽  
Gene Target ◽  
Gynecological Malignancy ◽  
Clonogenic Potential ◽  
Resistant Cells

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.

scholarly journals Insight into Cisplatin-Resistance Signaling of W1 Ovarian Cancer Cells Emerges mTOR and HSP27 as Targets for Sensitization Strategies

2020 ◽  
Vol 21 (23) ◽  
pp. 9240
Author(s):  
Kathleen Wantoch von Rekowski ◽  
Philipp König ◽  
Svenja Henze ◽  
Martin Schlesinger ◽  
Piotr Zawierucha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Mapk Pathway ◽  
Ovarian Cancer Cells ◽  
Strong Impact ◽  
Intrinsic Resistance ◽  
Western Blots ◽  
Collagen Type 1 ◽  
Signaling Components

The microenvironment possesses a strong impact on the tumor chemoresistance when cells bind to components of the extracellular matrix. Here we elucidate the signaling pathways of cisplatin resistance in W1 ovarian cancer cells binding to collagen type 1 (COL1) and signaling interference with constitutive cisplatin resistance in W1CR cells to discover the targets for sensitization. Proteome kinase arrays and Western blots were used to identify the signaling components, their impact on cisplatin resistance was evaluated by inhibitory or knockdown approaches. W1 cell binding to COL1 upregulates integrin-associated signals via FAK/PRAS40/mTOR, confirmed by β1-integrin (ITGB1) knockdown. mTOR appears as key for resistance, its blockade reversed COL1 effects on W1 cell resistance completely. W1CR cells compensate ITGB1-knockdown by upregulation of discoidin domain receptor 1 (DDR1) as alternative COL1 sensor. COL1 binding via DDR1 activates the MAPK pathway, of which JNK1/2 appears critical for COL1-mediated resistance. JNK1/2 inhibition inverts COL1 effects in W1CR cells, whereas intrinsic cisplatin resistance remained unaffected. Remarkably, knockdown of HSP27, another downstream MAPK pathway component overcomes intrinsic resistance completely sensitizing W1CR cells to the level of W1 cells for cisplatin cytotoxicity. Our data confirm the independent regulation of matrix-induced and intrinsic chemoresistance in W1 ovarian cancer cells and offer novel targets for sensitization.

MiR-489 modulates cisplatin resistance in human ovarian cancer cells by targeting Akt3

2014 ◽  
Vol 25 (7) ◽  
pp. 799-809 ◽  
Author(s):  
Huijuan Wu ◽  
Zhenghua Xiao ◽  
Hua Zhang ◽  
Ke Wang ◽  
Wenxin Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer
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