Autophagic flux promotes cisplatin resistance in human ovarian carcinoma cells through ATP-mediated lysosomal function

  • Authors:
    • Liwei Ma
    • Ye Xu
    • Jing Su
    • Huimei Yu
    • Jinsong Kang
    • Hongyan Li
    • Xiaoning Li
    • Qi Xie
    • Chunyan Yu
    • Liankun Sun
    • Yang Li
  • View Affiliations

  • Published online on: September 21, 2015     https://doi.org/10.3892/ijo.2015.3176
  • Pages: 1890-1900
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Abstract

Lysosomes are involved in promoting resistance of cancer cells to chemotherapeutic agents. However, the mechanisms underlying lysosomal influence of cisplatin resistance in ovarian cancer remain incompletely understood. We report that, compared with cisplatin-sensitive SKOV3 cells, autophagy increases in cisplatin-resistant SKOV3/DDP cells treated with cisplatin. Inhibition of early‑stage autophagy enhanced cisplatin-mediated cytotoxicity in SKOV3/DDP cells, but autophagy inhibition at a later stage by disturbing autophagosome-lysosome fusion is more effective. Notably, SKOV3/DDP cells contained more lysosomes than cisplatin‑sensitive SKOV3 cells. Abundant lysosomes and lysosomal cathepsin D activity were required for continued autolysosomal degradation and maintenance of autophagic flux in SKOV3/DDP cells. Furthermore, SKOV3/DDP cells contain abundant lysosomal ATP required for lysosomal function, and inhibition of lysosomal ATP accumulation impaired lysosomal function and blocked autophagic flux. Therefore, our findings suggest that lysosomes at least partially contribute to cisplatin resistance in ovarian cancer cells through their role in cisplatin-induced autophagic processes, and provide insight into the mechanism of cisplatin resistance in tumors.
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November-2015
Volume 47 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ma L, Xu Y, Su J, Yu H, Kang J, Li H, Li X, Xie Q, Yu C, Sun L, Sun L, et al: Autophagic flux promotes cisplatin resistance in human ovarian carcinoma cells through ATP-mediated lysosomal function. Int J Oncol 47: 1890-1900, 2015.
APA
Ma, L., Xu, Y., Su, J., Yu, H., Kang, J., Li, H. ... Li, Y. (2015). Autophagic flux promotes cisplatin resistance in human ovarian carcinoma cells through ATP-mediated lysosomal function. International Journal of Oncology, 47, 1890-1900. https://doi.org/10.3892/ijo.2015.3176
MLA
Ma, L., Xu, Y., Su, J., Yu, H., Kang, J., Li, H., Li, X., Xie, Q., Yu, C., Sun, L., Li, Y."Autophagic flux promotes cisplatin resistance in human ovarian carcinoma cells through ATP-mediated lysosomal function". International Journal of Oncology 47.5 (2015): 1890-1900.
Chicago
Ma, L., Xu, Y., Su, J., Yu, H., Kang, J., Li, H., Li, X., Xie, Q., Yu, C., Sun, L., Li, Y."Autophagic flux promotes cisplatin resistance in human ovarian carcinoma cells through ATP-mediated lysosomal function". International Journal of Oncology 47, no. 5 (2015): 1890-1900. https://doi.org/10.3892/ijo.2015.3176