Inhibition of Uncoupling Protein 2 Enhances the Radiosensitivity of Cervical Cancer Cells by Promoting the Production of Reactive Oxygen Species
Authors: Gang Zhao
Bao Sheng Sun
Xin Yu Dong
Yan Nan Shen
Xin Qiang Zhang
Zhe Hao Huang
Cui Hua Liu
Yuan Hang Li
Journal: Oxidative Medicine and Cellular Longevity (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: radiosensitivity; UCP2; cervical cancer; mitochondria; DNA damage
Affiliations: NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China., Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130031, China., Department of Radiotherapy, Tumor Hospital of Jilin Province, Changchun 130012, China.

Abstract:  Objective: The mechanism of enhanced radiosensitivity induced by mitochondrial uncoupling protein UCP2 was investigated in HeLa cells to provide a theoretical basis as a novel target for cervical cancer treatment. Methods: HeLa cells were irradiated with 4 Gy X-radiation at 1.0 Gy/min. The expression of UCP2 mRNA and protein was assayed by real-time quantitative polymerase chain reaction and western blotting. UCP2 siRNA and negative control siRNA fragments were constructed and transfected into HeLa cells 24 h after irradiation. The effect of UCP2 silencing and irradiation on HeLa cells was determined by colony formation, CCK-8 cell viability, γH2AX immunofluorescence assay of DNA damage, Annexin V-FITC/PI apoptosis assay, and propidium iodide cell cycle assay. The effects on mitochondrial structure and function were investigated with fluorescent probes including dichlorodihydrofluorescein diacetate (DCFH-DA) assay of reactive oxygen species (ROS), rhodamine 123, and MitoTracker Green assay of mitochondrial structure and function. Results: Irradiation upregulated UCP2 expression, and UCP2 knockdown decreased the survival of irradiated HeLa cells. UCP2 silencing sensitized HeLa cells to irradiation-induced DNA damage and led to increased apoptosis, cell cycle arrest in G2/M, and increased mitochondrial ROS. Increased radiosensitivity was associated with an activation of P53, decreased Bcl-2, Bcl-xl, cyclin B, CDC2, Ku70, and Rad51 expression, and increased Apaf-1, cytochrome c, caspase-3, and caspase-9 expression. Conclusions: UCP2 inhibition augmented the radiosensitivity of cervical cancer cells, and it may be a potential target of radiotherapy of advanced cervical cancer. 

Retracted: No

PubPeer comments:
 The authors in this paper considered the notion of u201c**T-spherical fuzzy numbers**u201d and their application to selection of photovoltaic cells. As introduced in Definition 1, a **T-spherical fuzzy number** is a triplet $$P=(m, i, n)$$ such that, with respect to a given $t$, $$m, i, n in [0,1] quad m^t+ i^t + n^t le 1$$ Some new operations on T-spherical fuzzy numbers, called Einstein interaction operations, are defined in Eq.(3) **without any justification.** According to eq.(3), for any $tge 1$, the multiplication operation for two T-spherical fuzzy numbers $(0,1,0)$ and $(0,0,1)$ is $$(0,1,0)otimes(0,0,1) = (0,1,1)$$ The result means that **the multiplication of two T-spherical fuzzy numbers may not be a T-spherical fuzzy number.** As a consequence, the aggregation operators defined in Section 4 are not sound. Can the authors address this issue? ![file] ![file] ,