Enhanced Growth inhibition by Combined Gene Transfer of p53 and p16INK4a in Adenoviral Vectors to Lung Cancer Cell Lines.

Choi, Seung Ho; Park, Kyung Ho; Seol, Ja Young; Yoo, Chul Gyu; Lee, Choon Taek; Kim, Young Whan; Han, Sung Koo; Shim, Young Soo

doi:2001.50.1.67

Tuberc Respir Dis > Volume 50(1); 2001 > Article

Original Article

Tuberculosis and Respiratory Diseases 2001;50(1):67-75.
DOI: https://doi.org/10.4046/trd.2001.50.1.67 Published online January 1, 2001.

Enhanced Growth inhibition by Combined Gene Transfer of p53 and p16INK4a in Adenoviral Vectors to Lung Cancer Cell Lines.

Seung Ho Choi, Kyung Ho Park, Ja Young Seol, Chul Gyu Yoo, Choon Taek Lee, Young Whan Kim, Sung Koo Han, Young Soo Shim

Abstract

BACKGROUND
Two tumor suppressor genes, p53 and p16, which have different roles in controlling the cell cycle and inducing apoptosis, are frequently inactivated during carcinogenesis including lung cancer. Single tumor suppressor gene therapies using tither with p53 or p16 have been studied extensively. However, there is a paucity of reports regarding a combined gene therapy using these two genes. METHODS: The combined effect of p53 and p16 gene transfer by the adenoviral vector on the growth of lung cancer cell lines and its interactive mechanism was investigated. RESULTS: An isobologram showed that the co-transduction of p53 and p16 exhibited a synergistic growth inhibitory effect on NCI H358 and an additive effect on NCI H23. Cell cycle analysis demonstrated the induction of a synergistic G1/S arrest by a combined p53 and p16 transfer. This synergistic interaction was again confirmed in a soft agar clonogenic assay. CONCLUSION: These observations suggest the potential of a p53 and p16 combination gene therapy as another potent strategy in cancer gene therapy.

Key Words: Adenovirus, Interaction, Isobologram, p53, p16, Lung cancer