Related Experiment Video

Updated: Aug 8, 2026

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
06:03

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression

Published on: January 19, 2019

Adenovirus-mediated p16INK4a gene expression radiosensitizes non-small cell lung cancer cells in a p53-dependent

S Kawabe1, J A Roth, D R Wilson

  • 1Department of Experimental Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston 77030, USA.

Oncogene
|December 5, 2000
PubMed

Insights

Adenovirus-mediated p16INK4a expression enhances radiation sensitivity in non-small cell lung cancer (NSCLC) cells with wild-type p53. This combination therapy may offer a new gene therapy strategy for specific NSCLC tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Therapy

Background:

  • Non-small cell lung cancer (NSCLC) often exhibits alterations in tumor suppressor genes like p16INK4a and p53.
  • Understanding the interplay between p16INK4a and p53 is crucial for developing effective NSCLC treatments.
  • Radiation therapy is a cornerstone of NSCLC treatment, but resistance remains a challenge.

Purpose of the Study:

  • To investigate the effect of adenovirus-mediated wild-type p16INK4a (Ad/p16) expression on the radiosensitivity of NSCLC cell lines.
  • To determine the role of endogenous p53 status in Ad/p16-mediated radiosensitization.
  • To explore the potential of Ad/p16 combined with radiation as a gene therapy approach for NSCLC.

Main Methods:

  • Utilized NSCLC cell lines with varying p53 statuses (wild-type, mutated, deleted).
  • Administered adenovirus-mediated p16INK4a (Ad/p16) or control (Ad/Luc) via transfection.
  • Assessed in vitro clonogenic survival and apoptosis induction following Ad/p16 and irradiation treatment.
  • Analyzed p53 protein expression using Western blotting.

Main Results:

  • Ad/p16 significantly enhanced radiosensitivity in A549 cells (wild-type p53) but not in H322 (mutated p53) or H1299 (deleted p53) cells.
  • Combination therapy (Ad/p16 plus irradiation) induced apoptosis, which was dependent on the endogenous p53 status.
  • Ad/p16 treatment increased p53 protein levels in A549 cells.
  • Restoring wild-type p53 in H1299 cells with Ad/p53, followed by Ad/p16, stabilized p53 and sensitized cells to radiation.

Conclusions:

  • Ad/p16-induced stabilization of p53 protein is a key mechanism in radiosensitization.
  • The combination of Ad/p16 and radiation shows promise as a gene therapy strategy for NSCLC tumors with wild-type p53 and nonfunctional p16INK4a.
  • This approach may overcome radioresistance by enhancing or restoring apoptosis pathways.

More Related Videos

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines09:45

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines

Published on: August 21, 2019

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes08:32

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

Published on: May 23, 2025

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...