Relationship between p21/WAF-1/CIP-1 and apoptosis in cervical cancer during radiation therapy

Int J Radiat Oncol Biol Phys. 1999 May 1;44(2):297-303. doi: 10.1016/s0360-3016(99)00026-7.

Abstract

Purpose: P21/WAF-1/CIP-1 was not considered to be involved in the regulation of apoptosis, an important indicator of radiosensitivity. However, it has been reported recently that apoptosis was suppressed when p21 expressed. The purpose of this study was to clarify the relationship between p21 and apoptosis and to evaluate the role of p21 in cervical cancer during radiation therapy (RT).

Methods and materials: Twenty-one patients with cervical cancer were treated by RT. Tissue samples were obtained from cervical tumors of all patients before RT, and 6 hours after the fifth dose of 1.8 Gy (5th Dose). Samples were subjected to nick end labeling for apoptosis and immunohistochemical staining for p21 and p53 antigen expression.

Results: The mean apoptotic index, p21 labeling index and p53 labeling index were 0.27%, 9.24% and 6.60%, respectively, before RT and increased significantly to 1.20%, 17.5% and 13.9%, respectively, after 5th Dose. The apoptotic index at 5th Dose was inversely correlated with the p21 labeling index (r = -0.50, p = 0.025). Furthermore, a positive correlation was observed between the p21 and p53 labeling indices both before RT and at 5th Dose (r = 0.52, p = 0. 02; r = 0.63, p < 0.01, respectively).

Conclusion: Our results demonstrate that apoptosis and expression of p21 and p53 were induced in cervical cancer during RT. p21 expression was dependent on p53 expression and moreover, it is suggested-that p21 might be a potential suppressor of radiation-induced apoptosis in cervical cancer during RT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • Cyclins / radiation effects
  • DNA Fragmentation
  • DNA, Neoplasm / radiation effects
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / radiation effects
  • Neoplasm Staging
  • Radiotherapy Dosage
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Protein p53 / radiation effects
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / physiopathology
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53