Improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells

被引：15

作者：

Razaghi, Ali ^{[1
]}

Villacres, Carina ^{[2
]}

Jung, Vincent ^{[2
]}

Mashkour, Narges ^{[1
]}

Butler, Michael ^{[2
]}

Owens, Leigh ^{[1
]}

Heimann, Kirsten ^{[1
]}

机构：

[1] James Cook Univ, Ctr Biodiscovery & Mol Dev Therapeut, Townsville, Qld 4811, Australia

[2] Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada

来源：

EXPERIMENTAL CELL RESEARCH | 2017年 / 359卷 / 01期

关键词：

Interferon gamma; Glycosylation; Ovarian cancer; SKOV3; FADD; Therapeutic efficacy; NF-KAPPA-B; IFN-GAMMA; INDUCED APOPTOSIS; PRODUCTION PLATFORMS; DEPENDENT APOPTOSIS; GROWTH-INHIBITION; MUSCLE-CELLS; FADD; GLYCOSYLATION; NECROPTOSIS;

D O I：

10.1016/j.yexcr.2017.08.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Human interferon gamma (hIFNy) affects tumour cells and modulates immune responses, showing promise as an anti-cancer biotherapeutic. This study investigated the effect of glycosylation and expression system of recombinant hIFNy in ovarian carcinoma cell lines, PEO1 and SKOV3. The efficacy of E. colt- and mammalian expressed hIFN gamma (hIFN gamma-CHO and HEK293, glycosylated/de-glycosylated) on cytostasis, cell death (MTT, and Guava-ViaCount flow-cytomeffy) and apoptotic signalling (Western blot of Cdk2, histone H3, procaspase-3, FADD, cleaved PARP, and caspase-3) was examined. Hydrophilic Interaction Liquid Chromatography determined the structure of N-linked glycans present in HEK293-expressed hIFNy (hIFN gamma-HEK). PEO1 was more sensitive hIFN gamma than SKOV3, but responses were dose-dependent and expression platform/glycosylation status-independent, whereas SKOV3 responded to mammalian-expressed hIFNy in a dose-independent manner, only. Complex-type oligosaccharides dominated the N-glycosylation pattern of hIFN gamma-HEK with some terminal sialylation and core fucosylation. Cleaved PARP and cleaved caspase-3 were not detected in either cell line, but FADD was expressed in SKOV3 with levels increased following treatment. In conclusion, hIFN gamma did not induce apoptosis in either cell line. Mammalian- expressed hIFNy increased cell death in the drug-resistant SKOV3. The presence of FADD in SKOV3, which may inhibit apoptosis through activation of NF-kappa B, could serve as a novel therapeutic target.

引用

页码：20 / 29

页数：10

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