Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2

  • Authors:
    • Jee-Eun Kim
    • Ji-In Lee
    • Dong-Hoon Jin
    • Wang Jae Lee
    • Ga Bin Park
    • Seonghan Kim
    • Yeong Seok Kim
    • T.-C. Wu
    • Dae Young Hur
    • Daejin Kim
  • View Affiliations

  • Published online on: March 12, 2014     https://doi.org/10.3892/or.2014.3082
  • Pages: 2429-2437
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Abstract

Interruption of the cell cycle is accompanied by changes in several related molecules that result in the activation of apoptosis. The present study was performed to verify the apoptotic effects of sequential treatment with bortezomib and celecoxib in TC-1 cells expressing the human papillomavirus (HPV) E6 and E7 proteins. In TC-1 cells sequentially treated with bortezomib and celecoxib, apoptosis was induced through decreased expression of signal transducer and activator of transcription-3 (STAT3), cyclin D1 and cyclin-dependent kinase (CDK) 2, which are major regulators of the G0/G1 cell cycle checkpoint. In addition, increased levels of p21, CHOP, BiP and p-p38 MAPK were identified in these cells. The treatment-induced apoptosis was effectively inhibited by treatment with SB203580, an inhibitor of p-p38. Moreover, the growth of tumors sequentially treated with bortezomib and celecoxib was retarded compared to the growth of tumors exposed to a single treatment with either bortezomib or celecoxib in vivo. We demonstrated that sequential treatment with bortezomib and celecoxib induced apoptosis via p-p38-mediated G0/G1 cell cycle arrest and endoplasmic reticulum (ER) stress. Sequential treatment with these two drugs could therefore be a useful therapy for cervical cancer.
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May-2014
Volume 31 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim J, Lee J, Jin D, Lee WJ, Park GB, Kim S, Kim YS, Wu T, Hur DY, Kim D, Kim D, et al: Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2. Oncol Rep 31: 2429-2437, 2014
APA
Kim, J., Lee, J., Jin, D., Lee, W.J., Park, G.B., Kim, S. ... Kim, D. (2014). Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2. Oncology Reports, 31, 2429-2437. https://doi.org/10.3892/or.2014.3082
MLA
Kim, J., Lee, J., Jin, D., Lee, W. J., Park, G. B., Kim, S., Kim, Y. S., Wu, T., Hur, D. Y., Kim, D."Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2". Oncology Reports 31.5 (2014): 2429-2437.
Chicago
Kim, J., Lee, J., Jin, D., Lee, W. J., Park, G. B., Kim, S., Kim, Y. S., Wu, T., Hur, D. Y., Kim, D."Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2". Oncology Reports 31, no. 5 (2014): 2429-2437. https://doi.org/10.3892/or.2014.3082