Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro.
BACKGROUND
The National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR) antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells.


METHODS
Human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and epidermal growth factor receptor (EGFR) were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR).


RESULTS
Propranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression.


CONCLUSIONS
Taken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway.
Liao
Xinhua
X
Department of General Surgery, First Affiliated Hospital of Medical College of Xi'an Jiao-Tong University, Yanta West Road 277, Xi'an 710061, PR China.
Che
Xiangming
X
Zhao
Wei
W
Zhang
Danjie
D
Long
Houlong
H
Chaudhary
Prakash
P
Li
Haijun
H
D000230:Adenocarcinoma; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D006801:Humans; D011433:Propranolol / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011878:Radiotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013274:Stomach Neoplasms
D014408:Biomarkers, Tumor; D011838:Radiation-Sensitizing Agents; D011433:Propranolol