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Combination of Th1 cytokines plus small molecule kinase inhibitors Palbociclib or Sunitinib potentiate apoptosis in breast cancer cell lines

Ghimirey, Nirmala

Abstract Details

2018, MS, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Vaccine-induced, Th1-polarized immunity can have a positive impact on early HER-2pos breast cancer, especially when combined with drugs that block estrogen signaling. This suggests that pharmacological targeting of additional intracellular signaling pathways could also potentiate vaccine effects. We therefore tested the chief cytokine effectors of Th1 immunity (IFN-gamma; and TNF-a) in combination with targeted drugs including palbociclib (cyclin-dependent kinase 4/6 inhibitor) and sunitinib (broad spectrum receptor tyrosine kinase inhibitor) on a panel of human breast cancer cell lines (MCF-7, SKBR-3, JIMT-1, HCC-1419, MDA-MB-468 and MDA-MB-231). After multiday exposure, we examined the impact of combinations of these agents on a wide variety of cellular characteristics including metabolic activity (Alamar Blue assay), cell viability (Trypan Blue staining), loss of mitochondrial membrane potential (TMRE staining), and indicators of apoptotic cell death (Annexin V/propidium iodide staining, and cytochrome c release). The overall findings were that combined treatments with Th1 cytokines plus individual targeted drugs had significantly greater impact on breast cancer cell function than either cytokines or drug alone. These data suggest that palbociclib and sunitinib should be further investigated as possible adjuvants to vaccine therapy for breast cancer.
Gary Koski, Ph.D (Advisor)
93 p.

Recommended Citations

Citations

  • Ghimirey, N. (2018). Combination of Th1 cytokines plus small molecule kinase inhibitors Palbociclib or Sunitinib potentiate apoptosis in breast cancer cell lines [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1530017347709489

    APA Style (7th edition)

  • Ghimirey, Nirmala. Combination of Th1 cytokines plus small molecule kinase inhibitors Palbociclib or Sunitinib potentiate apoptosis in breast cancer cell lines. 2018. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1530017347709489.

    MLA Style (8th edition)

  • Ghimirey, Nirmala. "Combination of Th1 cytokines plus small molecule kinase inhibitors Palbociclib or Sunitinib potentiate apoptosis in breast cancer cell lines." Master's thesis, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1530017347709489

    Chicago Manual of Style (17th edition)