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16 May 2019 : Laboratory Research  

Doxorubicin-Induced Cancer Cell Senescence Shows a Time Delay Effect and Is Inhibited by Epithelial-Mesenchymal Transition (EMT)

Xuerui Hu1ABCDEF, Hongqi Zhang2ACDEG*

DOI: 10.12659/MSM.914295

Med Sci Monit 2019; 25:3617-3623


BACKGROUND: Senescence is a natural barrier for the body to resist the malignant transformation of its own cells. This work investigated the senescence characteristics of cancer cells in vitro.

MATERIAL AND METHODS: Human cervical cancer HeLa cells were treated with different concentrations of doxorubicin for 3 days, with or without subsequent extended culture in drug-free medium for 6 days. Senescent cell ratios between these 2 culture schemes were calculated. Expression of 2 senescence-associated secretory factors, IL-6 and IL-8, were detected by RT-PCR and ELISA. Doxorubicin treatment induced epithelial-mesenchymal transition in cancer cells. The proportions of senescent cells in epithelial-like and mesenchymal-like sub-groups were calculated. Doxorubicin-treated HeLa cells were stained with Vimentin antibody and sorted by flow cytometry. Senescent cell marker p16ᴵᴺᴷ⁴ᵃ and IL-8 expression in Vimentin-high and Vimentin-low cells were detected by Western blot.

RESULTS: We found that less than 1% of HeLa cells showed senescence phenotype after treatment with doxorubicin for 3 days. However, the proportion of senescent cells was significantly increased when the doxorubicin-treated cells were subsequently cultured in drug-free medium for another 6d. RT-PCR and ELISA results showed that this prolonged culture method could further improve the expression of IL-6 and IL-8. We also found that the senescent cells were mainly epithelial-like type and few presented mesenchymal-like shape. p16ᴵᴺᴷ⁴ᵃ and IL-8 expression were decreased in cell fraction with higher Vimentin expression.

CONCLUSIONS: Our results suggested the existence of time delay effect in doxorubicin-induced senescence of HeLa cells, and epithelial- mesenchymal transition may resist doxorubicin-induced cell senescence.

Keywords: Cell Aging, Doxorubicin, Epithelial-mesenchymal transition, Hela Cells, Interleukin-6, Interleukin-8, Neoplasms, Time Factors, Vimentin



01 January 2023 : Editorial  

Editorial: Current Status of Two Adjuvanted Malaria Vaccines and the World Health Organization (WHO) Strategy to Eradicate Malaria by 2030

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.939357

Med Sci Monit 2023; 29:e939357


26 January 2023 : Editorial  

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Med Sci Monit In Press; DOI: 10.12659/MSM.939580  

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Med Sci Monit In Press; DOI: 10.12659/MSM.938606  

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20 Jan 2023 : Clinical Research  

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750