Open Access

Thrombopoietin protects H9C2 cells from excessive autophagy and apoptosis in doxorubicin‑induced cardiotoxicity

  • Authors:
    • Han Wang
    • Hua Wang
    • En‑Yu Liang
    • Li‑Xia Zhou
    • Zhan‑Ling Dong
    • Ping Liang
    • Qi‑Fang Weng
    • Mo Yang
  • View Affiliations

  • Published online on: November 14, 2017     https://doi.org/10.3892/ol.2017.7410
  • Pages:839-848
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: HTML 0 views | PDF 0 views
0

Abstract

Cardiac toxicity has been the major concern when using doxorubicin (DOX) in cancer therapy. Thrombopoietin (TPO) protects cardiac cells from DOX‑induced cell damage; however, its molecular mechanism remains exclusive. The anti‑autophagic and anti‑apoptotic effects of TPO upon DOX treatment were studied in the cardiac H9C2 cell line, with bafilomycin A1 treatment as a positive control for autophagy inhibition. Cell viability was measured by Cell Counting Kit‑8 assay in different treatment groups. The mRNA and/or protein levels of apoptotic markers and autophagy‑associated factors were detected. The mean number of microtubule‑associated protein 1A/1B‑light chain 3 (LC3) puncta per cell was quantified to indicate autophagosomes and autolysosomes, of which the ones co‑stained with lysosomal‑associated membrane protein 1 were considered as autolysosomes. DOX treatment (5 µg/ml, 24 h) significantly impaired H9C2 cell viability compared with the control, while TPO pretreatment (10 ng/ml, 36 h) improved cell viability upon DOX treatment. DOX exposure markedly increased LC3 puncta in H9C2 cells, and TPO pretreatment reduced the number of autophagosomes, but showed no significant inhibitory effect on autolysosome formation. The autophagy inhibition by TPO upon DOX treatment was confirmed according to protein quantification of LC3‑II and nucleoporin 62. TPO also suppressed autophagy‑promoting protein Beclin‑1, and elevated the anti‑autophagic factors GATA‑binding protein‑4 and B cell lymphoma‑2. Furthermore, TPO reduced DOX‑induced apoptosis in H9C2 cells, as reflected by the amount changes of caspase‑3. Taken together, these results revealed that TPO has a protective role in H9C2 cells from DOX‑induced autophagy as well as apoptosis, and indicated that TPO may act as a cardioprotective drug in DOX‑treated patients.

Related Articles

Journal Cover

January 2018
Volume 15 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wang, H., Wang, H., Liang, E., Zhou, L., Dong, Z., Liang, P. ... Yang, M. (2018). Thrombopoietin protects H9C2 cells from excessive autophagy and apoptosis in doxorubicin‑induced cardiotoxicity. Oncology Letters, 15, 839-848. https://doi.org/10.3892/ol.2017.7410
MLA
Wang, H., Wang, H., Liang, E., Zhou, L., Dong, Z., Liang, P., Weng, Q., Yang, M."Thrombopoietin protects H9C2 cells from excessive autophagy and apoptosis in doxorubicin‑induced cardiotoxicity". Oncology Letters 15.1 (2018): 839-848.
Chicago
Wang, H., Wang, H., Liang, E., Zhou, L., Dong, Z., Liang, P., Weng, Q., Yang, M."Thrombopoietin protects H9C2 cells from excessive autophagy and apoptosis in doxorubicin‑induced cardiotoxicity". Oncology Letters 15, no. 1 (2018): 839-848. https://doi.org/10.3892/ol.2017.7410