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

2016 ◽  
Vol 39 (3) ◽  
pp. 1098-1110 ◽  
Author(s):  
Chanjuan Li ◽  
Hongjuan Ding ◽  
Jing Tian ◽  
Lili Wu ◽  
Yun Wang ◽  
...  

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.

The Analyst ◽  
2018 ◽  
Vol 143 (24) ◽  
pp. 6087-6094 ◽  
Author(s):  
Khansa Al-Jorani ◽  
Anja Rüther ◽  
Rukshani Haputhanthri ◽  
Glen B. Deacon ◽  
Hsiu Lin Li ◽  
...  

ATR-FTIR spectroscopy has been applied to compare the effect of new organoamidoplatinum(ii) complexes with cisplatin on cells from a cisplatin-sensitive and a cisplatin-resistant ovarian cancer cell line.


2015 ◽  
Vol 11 (1) ◽  
pp. 75
Author(s):  
Xue-Mei Gong ◽  
Cheng-Jiu Hu ◽  
Quan-Jing Zhao ◽  
Dong-Mei Shi

<p>Polyphenolic compounds present in fruits, vegetables and grains are bioactive molecules which elicit a wide range of responses both in vivo and in vitro. The aim of this study was to investigate whether the soybean isoflavone Equol could induce apoptosis in ovarian cancer cells. In this study, we evaluated molecular events associated with apoptosis induced by Equol and paclitaxel (PTX) in an ovarian cancer cell line SKOV-3. To assess whether growth inhibition was due to apoptosis, flow cytometry, colorimetry experiments, immunoblot analyses through measuring DNA fragmentation, the level of TRAIL,the cleavage of poly(ADP-ribose) polymerase (PARP) and the activation of caspase-3, -8 and -9 were also performed. Additional markers of apoptosis were also measured like phosphatidylserine externalization and morphological changes. In addition, glycoprotein P (P-gp) activity in SKOV-3 ovarian cancer cell line was also estimated. The experimental results showed that apoptosis was induced by extrinsic pathway triggered by certain TNF family members. Overall results suggested that Equol induces apoptosis in SKOV-3 cells via a TRAIL and caspase 8-dependent pathway whereas paclitaxel leads to smaller apoptotic events when compared to that of Equol.</p>


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17559-e17559
Author(s):  
Warne Pedro Andrade ◽  
Bryan Ôrtero Perez Gonçalves ◽  
Luciana Maria Silva ◽  
Agnaldo Lopes Dasilva Filho

e17559 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with the presence of chemoresistance contributing to the poor prognosis. Approximately 80% of cases are diagnosed in stage III C and are treated with cytoreduction surgery followed by adjuvant chemotherapy. However, 70 percent of these patients have pelvic and peritoneal recurrences. Heat Shock Proteins are produced in response to pathophysiological stress and take part in several stages of carcinogenesis, acting primarily as anti-apoptotic agents. They are also implicated in resistance to chemotherapy in several types of tumors. In an attempt to improve oncological results, new therapeutic approaches such as intraperitoneal chemotherapy and HIPEC have been proposed in recent studies with gains in overall survival (OS). However, some questions have not yet been answered. Methods: in the study cultures of ovarian cancer cells were performed TOV-21G (clear cell carcinoma), SK-OV-3 (platinum-resistant serous carcinoma) and OV-90 (high-grade serous). Cell cytotoxicity (MTT) assay was performed. The ovarian cancer cells lines were treated with cisplatin in normothermia (37 degrees Celsius) and cisplatin in hyperthermia (41 degrees Celsius) and a control group treated with PBS saline solution at (37 degrees Celsius and 41 degrees Celsius) for 24 hours followed by new supplementation and a new 3-hours incubation. Clonogenic assay was performed. Then they were submitted to RNA extraction and reverse transcription. qRT-PCR was performed to compare the expression of TRAP1, HSPB1, HSPD1, HSPA1A, HSPA1L and ERCC1 in different treatments. Results: There was no statistical difference in relation to cytotoxicity between treatment with heated cisplatin compared to treatment with normothermia. It was not possible to evaluate the expression of the heat shock genes in the SK-OV3 lineage.The HSPB1, HSPD1, TRAP1 and ERCCC1 genes were positively regulated in OV-90 submitted to hyperthermia in relation to normothermia and there were no significant changes in expression in the TOV-21-G. Conclusions: In conclusion, we suggest that OV-90 Serous ovarian cancer cell line was more susceptibly at hyperthermia by cisplatin. The HSPA1A, HSPA1L, TRAP1 and HSPB1 heat shock genes and ERCC1 genes were upregulated in the heated cisplatin group and contribute to a poor prognosis related to resistance. The HSPB1 and ERCC1 genes had the greatest expression with 1000x higher.Thus, it is necessary to evaluate these genes in a clinical study of HIPEC.


Author(s):  
Yunjing Song ◽  
Jian Wang ◽  
Chunnian Zhang ◽  
Ying Yu ◽  
Hong Cai

IntroductionWe also investigated the Carpachromene in the cytotoxicity studies against common human ovarian cancer cell ‎line i.e., SW 626, in-vitro.Material and methodsCell viability of Carpachromene was very low against common ‎human ovarian cancer ‎cell line i.e. SW 626 without any cytotoxicity on normal cell line. To compare the ‎biological activities of molecules, the enzymes used are α-glucosidase, acetylcholinesterase, respectively. Finally, ‎calculations were made using the molecular docking method to compare the biological activity of the ‎carpachromene molecule. We then examined whether the release of Smac is necessary for apoptosis in ovarian ‎cancer cells using the SW 626‎ cell line. We first examined mitochondrial and cytosolic Smac levels after ‎Carpachromene treatment. ‎ResultsFollowing the docking calculations, the properties of the carpachromene molecule ‎were examined by ADME/T analysis in order to be used as a drug in the future. In addition, the anti-oxidant ‎properties of the molecules were examined in both gas and water phase with the HF/6-31g basis set with the ‎Gaussian software program. As shown, exposure of ovarian cancer cells to Carpachromene decreased ‎mitochondrial Smac and increased cytosolic Smac levels in a time-dependent fashion. As depicted in results, a ‎decrease in Smac expression was confirmed by Western blot. Silencing of Smac significantly inhibited ‎Carpachromene-induced caspase-3 cleavage and attenuated apoptosis in these cells Moreover, overexpression of ‎a Smac heptapeptide (Smac-N7) enhanced Carpachromene-induced cell deathConclusionsAccording to the above findings, the Carpachromene may be administrated for the treatment of several types of ‎human ovarian cancer in humans. ‎


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lixu Jin ◽  
Yuling Chen ◽  
Xinlin Mu ◽  
Qingquan Lian ◽  
Haiyun Deng ◽  
...  

Ovarian cancer is a major cause for death of gynecological cancer patients. The efficacy of traditional surgery and chemotherapy is rather compromised and platinum-resistant cancer recurs. Finding new therapeutic targets is urgently needed to increase the survival rate and to improve life quality of patients with ovarian cancer. In the present work, phosphoproteomic analysis was carried out on untreated and gossypol-treated ovarian cancer cell line, HOC1a. We identified approximately 9750 phosphopeptides from 3030 phosphoproteins, which are involved in diverse cellular processes including cytoskeletal organization, RNA and nucleotide binding, and cell cycle regulation. Upon gossypol treatment, changes in phosphorylation of twenty-nine proteins including YAP1 and AKAP12 were characterized. Western blotting and qPCR analysis were used to determine expression levels of proteins in YAP1-related Hippo pathway showing that gossypol induced upregulation of LATS1, which phosphorylates YAP1 at Ser 61. Furthermore, our data showed that gossypol targets the actin cytoskeletal organization through mediating phosphorylation states of actin-binding proteins. Taken together, our data provide valuable information to understand effects of gossypol on protein phosphorylation and apoptosis of ovarian cancer cells.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jing-Quan Wang ◽  
Zhuo-Xun Wu ◽  
Yuqi Yang ◽  
Jin-Sui Li ◽  
Dong-Hua Yang ◽  
...  

Ovarian cancer is one of the leading female malignancies which accounts for the highest mortality rate among gynecologic cancers. Surgical cytoreduction followed by chemotherapy is the mainstay of treatment. However, patients with recurrent ovarian cancer are likely to exhibit resistance to chemotherapy due to reduced sensitivity to chemotherapeutic drugs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been extensively studied as multidrug resistance (MDR) mediators since they are responsible for the efflux of various anticancer drugs. Multidrug resistance protein 7 (MRP7, or ABCC10) was discovered in 2001 and revealed to transport chemotherapeutic drugs. Till now, only limited knowledge was obtained regarding its roles in ovarian cancer. In this study, we established an MRP7-overexpressing ovarian cancer cell line SKOV3/MRP7 via transfecting recombinant MRP7 plasmids. The SKOV3/MRP7 cell line was resistant to multiple anticancer drugs including paclitaxel, docetaxel, vincristine and vinorelbine with a maximum of 8-fold resistance. Biological function of MRP7 protein was further determined by efflux-accumulation assays. Additionally, MTT results showed that the drug resistance of the SKOV3/MRP7 cells was reversed by cepharanthine, a known inhibitor of MRP7. Moreover, we also found that the overexpression of MRP7 enhanced the migration and epithelial-mesenchymal transition (EMT) induction. In conclusion, we established an in vitro model of MDR in ovarian cancer and suggested MRP7 overexpression as the leading mechanism of chemoresistance in this cell line. Our results demonstrated the potential relationship between MRP7 and ovarian cancer MDR.


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