Abstract
We have previously shown that pachymic acid (PA) inhibited tumorigenesis of gastric cancer (GC) cells. However, the exact mechanism underlying the radiation response of GC was still elusive. To evaluate the effects of PA treatment on radiation response of GC cell lines both in vitro and in vivo, a colony formation assay and xenograft mouse model were employed. Changes in Bax and HIF1ααexpressions were assessed in GC cells following PA treatment. Luciferase reporter and chromatin immune-precipitation assays were carried out to investigate the regulation of Bax through HIF1αα. Stable HIF1αα knockdown was introduced into GC cells to further study the mechanism underlying PA-enhanced response to radiation both in vitro and in vivo. PA greatly enhanced the sensitivity of GC cells to radiation in vitro and in vivo, upregulated Bax expression and inhibited hypoxia. Bax expression was under hypoxia inhibition, and PA increased Bax expression through repressing HIF1αα. Stable HIF1ααoverexpression in GC cells abolished the sensitizing effect of PA on GC cells to radiation both in vitro and in vivo. PA functions as a radiation sensitizing compound in GC. PA treatment induces the expression of pro-apoptotic factor Bax by inhibiting hypoxia/HIF1αα, supporting the therapeutic potential of PA in radiation therapy against GC.
… PA Treatment
PA powder was obtained from Chengdu
Biopurify Phytochemicals
Ltd (Chengdu, China) (purity 98%) and reconstituted in dimethyl sulfoxide
(Sigma-Aldrich, St. Louis, MI, USA) to a stock concentration of 30 mM …
