Phenotypic Characteristics of Dormant Human Non-Small Cell Lung Cancer Cells Surviving Multifraction X-Ray Irradiation

Bull Exp Biol Med. 2022 Nov;174(1):76-80. doi: 10.1007/s10517-022-05652-7. Epub 2022 Nov 28.

Abstract

Phenotypic characteristics of human non-small cell lung cancer cells, A549 (p53 wild-type) and H1299 (p53-deficient) as well as their descendants surviving after multifraction X-ray irradiation at a cumulative dose of 60 Gy (sublines A549HR and H1299HR, respectively) were studied before and after additional 2 Gy single dose irradiation. In 24 h after the additional irradiation, we observed a significant increase in the proportion of cells with signs of entosis (by 5 times, p<0.05) and SA-β-gal+ cells (by 1.6 times, p<0.01) in the general population of A549HR cells. In contrast, a significant increase in the proportion of only SA-β-gal+ multinucleated giant cancer cells was revealed in the parental A549 cells. Additional single dose irradiation resulted in a significant (by 1.8 times, p<0.05) increase in the proportion of multinucleated giant cancer cells in H1299HR cells in comparison with their parental H1299 cells. These changes did not correlate with changes in the proportion of entotic cells, because their high basal content in the absence of functional p53 did not change in response to additional single dose irradiation. At the same time, both p53-deficient non-small cell lung cancer cell lines showed a significant (2.9-fold for H1299 and 5.5-fold for H1299HR cells, p<0.001) increase in the proportion of SA-β-gal+ cells in the general population, but not in the multinucleated giant cancer cells population.

Keywords: cell senescence; entosis; multinucleated giant cancer cells; non-small cell lung cancer; radioresistance.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / radiotherapy
  • Tumor Suppressor Protein p53 / genetics
  • X-Rays

Substances

  • Tumor Suppressor Protein p53