Sun Jian, Liu Ning-Bo, Zhuang Hong-Qing, Zhao Lun-Jun, Yuan Zhi-Yong, Wang Ping
Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.
Cancer Biomark. 2017;19(1):45-50. doi: 10.3233/CBM-160323.
Radiosensitivity by blocking the epidermal growth factor receptor and cyclooxygenase-2 pathways with erlotinib and celecoxib in A549 human lung cancer cell was investigated.
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.
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).
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.
研究了厄洛替尼和塞来昔布通过阻断表皮生长因子受体和环氧合酶-2途径对A549人肺癌细胞的放射敏感性。
采用MTT法检测厄洛替尼和塞来昔布对A549细胞的抗肿瘤作用。采用集落形成试验评估抗肿瘤作用。采用流式细胞术分析评估细胞周期和细胞凋亡，并进行蛋白质印迹分析以评估AKT和磷酸化AKT的表达。
厄洛替尼或塞来昔布均以剂量依赖性方式抑制A549细胞增殖。厄洛替尼或塞来昔布与放疗联合可抑制细胞集落形成，且厄洛替尼或塞来昔布与放疗联合的Dq、D0、SF2低于厄洛替尼或塞来昔布与放疗单独使用时（t = 6.62，P < 0.05）。塞来昔布或厄洛替尼以及塞来昔布和厄洛替尼联合放疗的增敏比分别为1.299、1.503和2.217。流式细胞术分析结果显示，塞来昔布或厄洛替尼均可诱导G0/G1期阻滞，并降低S期细胞比例，尤其是厄洛替尼-塞来昔布与放疗联合时。塞来昔布或厄洛替尼均可增强放疗诱导的细胞凋亡，尤其是厄洛替尼-塞来昔布与放疗联合时更为显著。此外，放疗可促进pAKT的表达，且厄洛替尼-塞来昔布与放疗联合组的pAKT显著最低（t = 4.89，P < 0.05）。
阻断EGFR和COX-2相关途径可增强放疗的抗肿瘤作用。其潜在机制包括增强细胞凋亡和放疗诱导的G0/G1期阻滞，可能是通过抑制PI3K/AKT信号通路实现的。
