Effects of CKMT1 on radiosensitivity of nasopharyngeal carcinoma cells

Int J Radiat Biol. 2019 May;95(5):597-606. doi: 10.1080/09553002.2019.1554919. Epub 2019 Jan 4.

Abstract

Purpose: Radioresistance is an important factor for unsatisfactory prognosis in Nasopharyngeal carcinoma (NPC) patients. Ubiquitous mitochondrial creatine kinase (CKMT1) is always associated with malignancy in a variety of cancers. However, its significance in NPC progression and radiosensitivity remains unclear. The present study focused on investigating the effects of CKMT1 on NPC cell radiosensitivity.

Material and methods: CKMT1 was overexpressed in NPC cell line CNE-1 or knocked out in CNE-2. Biological changes were detected after cells exposing to different doses of X-ray to determine the role of CKMT1 on NPC cell radiosensitivity.

Results: CKMT1 promotes proliferation and migration in NPC cell lines CNE-1 and CNE-2. Overexpression of CKMT1 in CNE-1 cells enhanced colony formation rates, reduced G2/M phase cell cycle arrest, lowered apoptosis rate and c-PARP level, and elevated STAT3 phosphorylation level after radiation treatment. While knocking out CKMT1 using the CRISPR/Cas9 system in CNE-2 cells lowered colony formation rates, increased G2/M phase cell cycle arrest, apoptosis rates, and c-PARP levels, and decreased STAT3 phosphorylation in response to radiation treatment.

Conclusions: NPC cells with higher CKMT1 exhibited lower radiosensitivity through promoting phosphorylation of STAT3. Our findings suggest that CKMT1 may be an alternative radiotherapeutic target in NPC therapy.

Keywords: CKMT1; nasopharyngeal carcinoma; radiosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Cell Division / radiation effects
  • Cell Line, Tumor
  • Cell Movement / radiation effects
  • Cell Proliferation / radiation effects
  • Creatine Kinase / deficiency
  • Creatine Kinase / genetics
  • Creatine Kinase / metabolism*
  • G2 Phase / radiation effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Gene Knockout Techniques
  • Humans
  • Nasopharyngeal Carcinoma / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiation Tolerance*

Substances

  • RNA, Messenger
  • CKMT1A protein, human
  • Creatine Kinase