Solitomab, an EpCAM/CD3 bispecific antibody (BiTE®), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo

2014 ◽  
Vol 133 ◽  
pp. 98
Author(s):  
D.P. English ◽  
C.L. Schwab ◽  
D.M. Roque ◽  
S. Bellone ◽  
E.S. Ratner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Bispecific Antibody ◽  
Ovarian Cancer Cell ◽  
Ex Vivo ◽  
Highly Active ◽  
Ovarian Cancer Cell Lines

Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts

2004 ◽  
Vol 14 (5) ◽  
pp. 824-831 ◽  
Author(s):  
E. S. Van Laar ◽  
E. Izbicka ◽  
S. Weitman ◽  
L. Medina-Gundrum ◽  
J. R. Macdonald ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Antitumor Activity ◽  
Tumor Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Tumor ◽  
Ovarian Cancer Cell ◽  
Human Tumor ◽  
Ovarian Cancer Cell Lines

The objective of this study was to investigate the cytotoxic activity of irofulven (HMAF, MGI 114), a unique chemotherapeutic agent currently under clinical investigation, in various preclinical models of ovarian cancer. Antiproliferative effects of irofulven in ovarian cancer cell lines and ovarian tumor specimens were characterized in vitro using sulforhodamine B and human tumor colony-forming assays, respectively. Irofulven demonstrated marked activity against a panel of ovarian tumor cell lines, including IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, and SK-OV-3, all of which exhibit various drug resistance mechanisms. In human tumor cloning assays, irofulven inhibited colony formation in surgically derived ovarian tumors at concentrations as low as 0.001 μg /ml and indicated superior activity in comparison with paclitaxel when tested against the same tumor specimens. The antitumor activity of irofulven compared to that of paclitaxel was also examined using the SK-OV-3 xenograft model. In mice bearing subcutaneously implanted SK-OV-3 tumors, treatment with paclitaxel failed to inhibit tumor growth; whereas mice treated with maximum tolerated doses of irofulven had a 25% partial shrinkage rate, and the remaining animals had a mean tumor growth inhibition of 82%. The potent activity of irofulven against ovarian tumors in vitro and in vivo supports the evaluation of its clinical activity in ovarian cancer.

scholarly journals miR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy

2021 ◽  
Author(s):  
Yang Zhou ◽  
Chunyan Wang ◽  
Jinye Ding ◽  
Yaoqi Sun ◽  
Zhongping Cheng
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cell Lines

Abstract Background Accumulating evidences reveal that aberrant microRNAs (miRNAs) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. Emerging evidences have demonstrated that miR-133a participates in tumorigenesis of various cancers. However, whether miR-133a is associated with cisplatin resistance in ovarian cancer remains unclear. Objective To investigate the role of miR-133a in the development of cisplatin resistance in ovarian cancer. Methods MiR-133a expression in cisplatin-resistant ovarian cancer cell lines was assessed by reverse-transcription quantitative PCR (RT-qPCR). Cell counting kit-8 (CCK-8) assay was used to evaluate cell viability of tumor cells treated with cisplatin in the presence or absence of miR-133a. Luciferase reporter assay was used to analyze binding of miR-133a with 3’ untranslated regions (3’UTR) of YES proto-oncogene 1 (YES1). The YES1 expression level was analyzed using the dataset from the international cancer genome consortiu (ICGC) and assessed by RT-qPCR and western blotting in vitro. The roles and mechanisms of YES1 on cell functions were further probed via gain- and loss-of-function analysis. Results The expression of miR-133a was significantly decreased in cisplatin resistant ovarian cancer cell lines (A2780-DDP and SKOV3-DDP), and the overexpression of miR-133a mimic reduced cisplatin resistance in A2780-DDP and SKOV3-DDP cells and the treatment of miR-133a inhibitor increased cisplatin sensitive in normal A2780 and SKOV3 cells. MiR-133a binds 3’UTR of YES1 and down-regulates its expression. Bioinformatics analysis revealed that YES1 expression was upregulated in recurrent cisplatin resistance ovarian cancer tissue and in vitro experiments also verified its upregulating in cisplatin resistance cell lines. Furthermore, we discovered that miR-133a down-regulated the expression of YES1 and thus inhibited the cell autophagy to reduce cisplatin resistance. Yes1 knockdown significantly suppressed the cisplatin resistance of ovarian cancer cells through inhibiting autophagy in vitro. Xenograft tumor implantation further demonstrated that Yes1 overexpression promoted ovarian tumor development and cisplatin resistance. Conclusion Our results suggest that miR-133a/YES1 axis plays a critical role in cisplatin resistance in human ovarian cancer by regulating cell autophagy, which might serve as a promising therapeutic target for ovarian cancer chemotherapy treatment in the future.

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