Baicalein modulates the radiosensitivity of cervical cancer cells in vitro via miR-183 and the JAK2/STAT3 signaling pathway

Adv Clin Exp Med. 2021 Jul;30(7):727-736. doi: 10.17219/acem/135478.

Abstract

Background: Increasing radiosensitivity of cancer cells can enhance the efficacy of cervical cancer treatment.

Objectives: This study evaluated the potential roles and mechanism of baicalein in regulating the radiosensitivity of cervical cancer cells in vitro.

Material and methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess miR-183 expression in End1/E6E7 cells, Hela cells and Hela cells irradiated with X-ray (0 Gy, 1 Gy, 3 Gy, 5 Gy, and 10 Gy). Cell Counting Kit-8 (CCK-8) method measured cell viability of Hela cells after miR-183 regulation, baicalein or RO8191 treatment. Apoptosis rates were detected using flow cytometry. Thereafter, expression of Bcl-2, Bax and caspase-3 RNA was also detected through RT-qPCR. Protein concentrations of E-cadherin, N-cadherin, Vimentin in epithelial-mesenchymal transition (EMT), phospho-JAK2/STAT3, and total Janus kinase 2/signal transducer and activator of transcription 3 STAT3 (JAK2/STAT3) were examined using enzyme-linked immunosorbent assay (ELISA) methods. RO8191, a JAK2/STAT3 activator, was used to activate the JAK2/STAT3 signaling pathway.

Results: The miR-183 expression was significantly lower in Hela cells compared to End1/E6E7 cells. Following upregulation of miR-183 in Hela cells, cell viability was inhibited while apoptosis was promoted. Moreover, EMT was inhibited after miR-183 over-expression. X-ray treatment markedly reduced the cell survival rate and increased miR-183 RNA expression. Baicalein treatment severely reduced the cell viability of 10-Gy X-ray-irradiated Hela cells, partially reversing the effect of miR-183, and also increased apoptosis and prevented EMT in irradiated cells. Y1007/8 in JAK2 and tyrosine (Tyr) residue 705 of STAT3 were phosphorylated, resulting in high expression of JAK2/STAT3, which was decreased by irradiation and baicalein treatment. RO8191 activated JAK2/STAT3 signaling, promoted cell viability and EMT, and inhibited cell apoptosis, while baicalein partly reversed the functions of RO8191.

Conclusions: Baicalein inhibited cell viability and EMT, and induced cell apoptosis of Hela cells, through upregulating miR-183 via inactivation of the JAK2/STAT3 signaling pathway.

Keywords: JAK2/STAT3; baicalein; irradiation; miR-183.

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Female
  • Flavanones
  • HeLa Cells
  • Humans
  • Janus Kinase 2
  • MicroRNAs* / genetics
  • Naphthyridines
  • Oxadiazoles
  • Radiation Tolerance
  • STAT3 Transcription Factor
  • Signal Transduction
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / radiotherapy

Substances

  • CDM-3008
  • Flavanones
  • MIRN183 microRNA, human
  • MicroRNAs
  • Naphthyridines
  • Oxadiazoles
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • baicalein
  • JAK2 protein, human
  • Janus Kinase 2