The expression of platelet-activating factor receptor modulates the cisplatin sensitivity of ovarian cancer cells: a novel target for combination therapy

Background/Aims: Epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating cancer progression. Snail1 has a pivotal role in the regulation of EMT, involving the loss of E-cadherin and concomitant upregulation of vimentin, among other biomarkers. We have found FSCN1 promoted EMT in ovarian cancer cells, but the precise mechanism of FSCN1 in EMT process has not been clearly elucidated. Methods: The levels of FSCN1 and snail1 were determined in epithelial ovarian cancer(EOC) specimen and in ovarian cancer cells by RT-qPCR. The changes of EMT makers and effects on snail1 by FSCN1 were examined by overexpression or depletion of FSCN1 in EOC cells by RT-qPCR and western blotting. The invasiveness of the FSCN1-modified EOC cells was examined in transwell assay. Co-immunoprecipitation (IP) was performed to detect the interaction between snail1 and FSCN1 in EOC cells. Results: We found FSCN1 and snail1 significantly increased in EOC, and especially in EOC with metastasis. FSCN1 was positively correlated with snail1 expression at the cellular/histological levels. Moreover, we further showed that FSCN1 physiologically interacted with and increased the levels of snail1 to promote ovarian cancer cell EMT. Conclusion: FSCN1 promote EMT through snail1 in ovarian cancer cells. FSCN1 is an attractive novel target for inhibiting invasion and metastasis of EOC cells.

Download Full-text

Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells

PLoS ONE ◽

10.1371/journal.pone.0132337 ◽

2015 ◽

Vol 10 (7) ◽

pp. e0132337 ◽

Cited By ~ 10

Author(s):

Dong-Jun Qin ◽

Cai-Xia Tang ◽

Li Yang ◽

Hu Lei ◽

Wei Wei ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Target Molecule ◽

Novel Target

Download Full-text

Promotion of Cell Death in Cisplatin-Resistant Ovarian Cancer Cells through KDM1B-DCLRE1B Modulation

International Journal of Molecular Sciences ◽

10.3390/ijms20102443 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2443 ◽

Cited By ~ 2

Author(s):

Yeon Kyu Lee ◽

Jinyeong Lim ◽

So Young Yoon ◽

Jong Cheon Joo ◽

Soo Jung Park ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Ovarian Cancer Cells ◽

Repair Gene ◽

Gynecological Malignancy ◽

Downstream Target ◽

Dna Repair Gene ◽

Cisplatin Sensitivity

Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.

Download Full-text