Molecular radiobiologyInhibition of STAT-3 results in radiosensitization of human squamous cell carcinoma☆
Section snippets
Cell culture
A431 human epidermoid cancer cells were obtained from American Type Culture Collection (Manassas, VA) and processed for cell culture as described in the previous studies from our laboratory [14]. Briefly, the cell lines were maintained in Dulbeco’s modified Eagle’s medium: F12 (50:50) containing 7% fetal bovine serum supplemented with l-glutamine and were incubated at 37 °C in 5% CO2.
Cell proliferation
This assay of daily growth was performed as previously described [10], [12]. Following the plating of A431 cells,
Results
Since activated STAT-3 is an important regulator of tumor growth and portends resistance to apoptosis in tumor cells, it was hypothesized that the inhibition of STAT-3, through the use of small interfering RNA (siRNA), may potentiate the effects of radiation in A431 human squamous cell carcinoma cells. In fact, when cells were transfected with 100 nM siRNA, using Oligofectamine, for as little as 4 h prior to various doses of radiation, the cells were significantly more responsive to the cytotoxic
Discussion
Although constitutive activation of STAT-3 has been shown to be characteristic of many tumors [6], [7], additional studies have shown that STAT-3 is greatly influenced by several upstream regulators of tumor growth [8], [11]. For instance, STAT-3 plays an important role in transmitting the growth signals that are initiated at the level of EGFr [3], [4], [5], [8]. EGFr is also known to be overexpressed in many tumors and the inhibition of EGFr has been shown to enhance the effects of
Acknowledgement
This study was supported in part by NIH R01 CA89297.
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Presented at the 11th International Wolfsberg Meeting, 2009.