University of South Alabama

Inhibition of Gli1 Increases Sensitivity to Cisplatin



Platinum-based anticancer agents are among the most widely used agents in clinical oncology. Nucleotide excision repair (NER) is the pathway through which platinum–DNA damage is repaired and, ERCC1 is a useful biomarker for the NER process in human cells. Understanding the molecular and pharmacological control of NER may allow for a more complete understanding of the modes of cellular and clinical resistance to this class of agents. In addition, such information may contribute to the development of non-platinum agents that damage DNA and/or modulate DNA repair.



Inventors at the University of South Alabama have identified that anti-Gli1 shRNA transfection into cisplatin-resistant human ovarian cancer cells results in a series of specific events. The c-jun protein cascade is switched on and cisplatin induction of ERCC1, XPA, and XRCC1 is blocked. Repair of platinum–DNA adduct is reduced by >60%; and the cells become more sensitive to cisplatin by a factor of six, with a change in the IC50 from 30 μm to 5 μm. Furthermore, when Hedgehog is inhibited at the level of the cell membrane, cellular sensitivity is not altered. This distinction may prove quite important in the development of pharmacological treatment strategies for cancer, where cisplatin resistance is a substantive clinical issue.



•  Repair of platinum–DNA adduct is reduced by >60%

•  Cells become more sensitive to cisplatin by a factor of six



Patent Issued


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Patent Information:
For Information, Contact:
Andrew Byrd
University of South Alabama
Eddie Reed
Rajeev Samant