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Article

Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78

  • Authors:
    • Wei Li
    • Wei Wang
    • Hong Dong
    • Yan Li
    • Li Li
    • Linfei Han
    • Zhiqiang Han
    • Shixuan Wang
    • Ding Ma
    • Hui Wang
  • View Affiliations / Copyright

    Affiliations: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China, Shanghai First Maternity and Infant Health Hospital, Tongji University, Shanghai 200040, P.R. China
  • Pages: 2525-2534
    |
    Published online on: April 23, 2014
       https://doi.org/10.3892/or.2014.3147
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Abstract

Glucose-regulated protein 78 (GRP78), the most abundant and well-characterized glucose-regulated protein, is a major stress-inducible chaperone localized to the endoplasmic reticulum (ER). The purpose of the present study was to investigate the mechanisms of GRP78 involved in the senescence sensitivity of ovarian cancer cells to cisplatin. In the present study, we found that the chemotherapy-sensitive ovarian tumor sections showed strong staining for heterochromatin protein 1-γ (HP1-γ), but weak staining for GRP78. Cisplatin-sensitive A2780 cells with low expression of GRP78 tended to undergo senescence easily when compared with the cisplatin-resistant C13K cells following a dose-gradient cisplatin exposure. Forced overexpression of GRP78 protected the cisplatin-sensitive A2780 cells from cisplatin-induced senescence through P53 and CDC2. Knockdown of GRP78 rescued the senescence sensitivity of cisplatin-resistant C13K cells to cisplatin through P21 and CDC2. Twisting of Ca2+ release from ER stores by GRP78 was established to be associated with the sensitivity of cisplatin-induced senescence in ovarian cancer cell lines. In conclusion, GRP78 may have anti-senescence effects on ovarian cancer cells involving multiple mechanisms. Intervention against GRP78 may reduce cisplatin resistance in ovarian cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Li W, Wang W, Dong H, Li Y, Li L, Han L, Han Z, Wang S, Ma D, Wang H, Wang H, et al: Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78. Oncol Rep 31: 2525-2534, 2014.
APA
Li, W., Wang, W., Dong, H., Li, Y., Li, L., Han, L. ... Wang, H. (2014). Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78. Oncology Reports, 31, 2525-2534. https://doi.org/10.3892/or.2014.3147
MLA
Li, W., Wang, W., Dong, H., Li, Y., Li, L., Han, L., Han, Z., Wang, S., Ma, D., Wang, H."Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78". Oncology Reports 31.6 (2014): 2525-2534.
Chicago
Li, W., Wang, W., Dong, H., Li, Y., Li, L., Han, L., Han, Z., Wang, S., Ma, D., Wang, H."Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78". Oncology Reports 31, no. 6 (2014): 2525-2534. https://doi.org/10.3892/or.2014.3147
Copy and paste a formatted citation
x
Spandidos Publications style
Li W, Wang W, Dong H, Li Y, Li L, Han L, Han Z, Wang S, Ma D, Wang H, Wang H, et al: Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78. Oncol Rep 31: 2525-2534, 2014.
APA
Li, W., Wang, W., Dong, H., Li, Y., Li, L., Han, L. ... Wang, H. (2014). Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78. Oncology Reports, 31, 2525-2534. https://doi.org/10.3892/or.2014.3147
MLA
Li, W., Wang, W., Dong, H., Li, Y., Li, L., Han, L., Han, Z., Wang, S., Ma, D., Wang, H."Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78". Oncology Reports 31.6 (2014): 2525-2534.
Chicago
Li, W., Wang, W., Dong, H., Li, Y., Li, L., Han, L., Han, Z., Wang, S., Ma, D., Wang, H."Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78". Oncology Reports 31, no. 6 (2014): 2525-2534. https://doi.org/10.3892/or.2014.3147
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