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Breit Thesis 2014 final.pdf (859.8 KB)

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Biologic Activity of the Novel SINE Compound KPT-335 Against Canine Melanoma Cell Lines

Breit, Megan N
http://rave.ohiolink.edu/etdc/view?acc_num=osu1397238345

Abstract Details

2014, Master of Science, Ohio State University, Veterinary Clinical Sciences.
Background: Exportin 1 (XPO1, also known as CRM1), is a protein responsible for the export of over 200 target proteins out of the nucleus. XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. Results: We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation and induced apoptosis of treated cells. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines induced the expression of the tumor suppressors p53 and p21, with enhanced nuclear localization. Conclusion: KPT-335 demonstrates biologic activity against canine melanoma cell lines at physiologically relevant doses, suggesting that KPT-335 may represent a viable treatment option for dogs with malignant melanoma.
Cheryl London, DVM, PhD (Advisor)
William Kisseberth, DVM, PhD (Advisor)
Emma Warry, BVSc (Hons) (Committee Member)
53 p.
Animal Diseases; Animal Sciences; Veterinary Services
Canine; Melanoma; CRM1; XPO1; SINE; KPT

Recommended Citations

Citations

  • Breit, M. N. (2014). Biologic Activity of the Novel SINE Compound KPT-335 Against Canine Melanoma Cell Lines [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397238345

    APA Style (7th edition)

  • Breit, Megan. Biologic Activity of the Novel SINE Compound KPT-335 Against Canine Melanoma Cell Lines. 2014. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1397238345.

    MLA Style (8th edition)

  • Breit, Megan. "Biologic Activity of the Novel SINE Compound KPT-335 Against Canine Melanoma Cell Lines." Master's thesis, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397238345

    Chicago Manual of Style (17th edition)

osu1397238345
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© 2014, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.