More than 50% of human tumors contain a mutation in p53. Over 90% of tumors are solid tumors. Solid tumors have low oxygenated regions, called hypoxic regions where the tumor cells are more resistant to radio- and chemo-therapy than their well-oxygenated counterparts. In this study, we constructed a cell-permeable p53 fusion protein with selective stability in the hypoxic region. The fusion protein contained the TAT peptide for transduction across membranes, the oxygen-dependent degradation domain of hypoxia-inducible factor-1alpha and wild-type p53. This protein was effectively delivered into tumor cells where it exerted anticancer activity leading to the inhibition of cancer cell growth in vitro and the reduction of tumor weight in vivo. Hence, the fusion protein can be a novel protein drug for antitumor therapies, especially for hypoxic tumor cells.
Bibliographical noteFunding Information:
We are grateful to the Beijing Center of Disease Prevention and Control for the gift of B16 mouse melanoma cells. This work was supported by a Grant from the National Natural Science Foundation of China (NO. 30572207).
- Cancer therapy
- Hypoxia-inducible factor-1α
- Oxygen-dependent degradation domain
- Solid tumors