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Rapamycin Reduces Cervical Cancer Cells Viability in Hypoxic Condition: Investigation of the Role of Autophagy and Apoptosis

Authors Rezazadeh D, Norooznezhad AH, Mansouri K, Jahani M, Mostafaie A, Mohammadi MH, Modarressi MH

Received 15 February 2020

Accepted for publication 28 April 2020

Published 18 May 2020 Volume 2020:13 Pages 4239—4247

DOI https://doi.org/10.2147/OTT.S249985

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Yao Dai


Davood Rezazadeh,1,2 Amir Hossein Norooznezhad,2 Kamran Mansouri,2 Mozhgan Jahani,2 Ali Mostafaie,2 Mohammad Hossein Mohammadi,3 Mohammad Hossein Modarressi1

1Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 3HSCT Research Center, Laboratory Hematology and Blood Banking Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran

Correspondence: Mohammad Hossein Modarressi Email modaresi@tums.ac.ir

Background: Rapamycin has been known as an anti-cancer agent that affects different malignancies such as glioblastoma and prostate cancer. However, there are few studies concerning rapamycin effects on the cervical cancer cells. In this study, it was aimed to investigate the possible effect of rapamycin on a cervical cancer cell line and explored the possible mechanism(s) and pathway(s) for this agent.
Materials and Methods: To do so, HeLa cells as cervical cancer cell line were used and treated with different concentrations of rapamycin under both normoxic and hypoxic conditions. Then, cell viability assays, Western blot, quantitative real-time polymerase chain reaction (QR-PCR), acridine orange and acridine orange/propidium iodide staining were performed to evaluate rapamycin effect on the mentioned cell line.
Results: The results showed that autophagy and apoptosis-related genes increased significantly in rapamycin-treated HeLa cells compared to controls. Moreover, cervical cancer cell death by rapamycin-induced autophagy in hypoxia was greater than normoxia compared with controls. In this study, it was showed that autophagy induction by rapamycin can mediate programmed cell death of cervical cancer cells, especially in hypoxic condition.
Conclusion: These findings provide a new evidence that rapamycin may inhibit hypoxic HeLa cell proliferation through the trigger of programmed cell death, facilitating the development of novel anti-cancer therapy.

Keywords: rapamycin, cervical cancer, autophagy, apoptosis, programed cell death

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