Affiliations: [a] Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China | [b] Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China | [c] Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
Correspondence:
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Corresponding author: Ping Wang, Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, No. 60 of Huanhuxi Road Hexi District, Tianjin 300060, China. Tel.: +86 22 23340123; E-mail:j_y_l726@sina.com
Abstract: BACKGROUND: Radiosensitivity by blocking the epidermal growth
factor receptor and cyclooxygenase-2 pathways with erlotinib and celecoxib
in A549 human lung cancer cell was investigated. METHODS: MTT assays were used to detect the antitumor effects of
erlotinib and celecoxib in A549 cells. Colony formation assays were used to
evaluate the antitumor effects. Flow cytometry analysis was used to assess
the cell cycle and cell apoptosis, and western blotting analysis was
performed to evaluate the expression of AKT and phosphorylated AKT. RESULTS: Either erlotinib or celecoxib inhibited the A549 cell
proliferation in a dose-dependent manner. Combining Erlotinib or celecoxib
with radiation can suppress the cell colony formation and the Dq, D0,
SF2 of the combining erlotinib or celecoxib with radiation was lower
than in the combinations either erlotinib or celecoxib with radiation (t= 6.62, P< 0.05). The SER of radiation with celecoxib or erlotinib and celecoxib and
erlotinib were 1.299, 1.503 and 2.217, respectively. The Flow cytometry
analysis results showed that either celecoxib or erlotinib could induce
G0/G1 arrest, and reduction of S phase cell proportion, especially
when combinations erlotinib-celecoxib with radiation. Either celecoxib or
erlotinib could enhance radiation-induced apoptosis, especially significant
when combinations erlotinib-celecoxib with radiation. Moreover, radiation
can promote the expression of pAKT, and the pAKT was remarkably lowest in
the combinations erlotinib-celecoxib with radiation group (t= 4.89, P< 0.05). CONCLUSIONS: Blocking both EGFR- and COX-2-related pathways could
enhance the antitumor effect of radiation. The underlying mechanisms
including the enhancement of apoptosis and radiation-induced G0/G1 arrest, possibly via inhibiting the PI3K/AKT signaling pathway.
