A novel EGFR-TKI inhibitor (cAMP-H(3)BO(3)complex) combined with thermal therapy is a promising strategy to improve lung cancer treatment outcomes.
A novel EGFR-TKI inhibitor (cAMP-H(3)BO(3)complex) combined with thermal therapy is a promising strategy to improve lung cancer treatment outcomes.
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新型EGFR-TKI抑制剂（cAMP-H(3)BO(3)复合物）与热疗法相结合是改善肺癌治疗结果的一种有前景的策略
DOI：
10.18632/oncotarget.17628
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发表时间：
2017-08-22
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
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作者：
Tong Y;Huang C;Zhang J
尽管EGFR-TKI（表皮生长因子受体酪氨酸激酶抑制剂）作为一线非小细胞肺癌治疗诱导了良好的反应，但耐药性仍然是一个严重的问题。同时，热疗法也显示出作为癌症治疗策略的前景。在这里，我们将联合收割机一种新的EGFR-TKI治疗与热疗法相结合，以改善肺癌的治疗结果。结果表明，cAMP-H3 BO 3复合物在体外有效抑制EGFR自身磷酸化，同时诱导凋亡和细胞周期阻滞。与阴性对照组相比，氧化磷酸化解偶联剂甲状腺素钠和cAMP-H_3BO_3复合物或cAMP-H_3BO_3复合物治疗组的肿瘤生长受到显著抑制（P < 0.05）。此外，甲状腺素钠治疗引起的体温升高抑制肿瘤生长。免疫组化结果显示，cAMP-H3 BO 3复合物加甲状腺素钠组A549细胞凋亡率明显高于其他各组。此外，Ca 2+含量分析显示，cAMP-H3 BO 3复合物加甲状腺素钠治疗组肿瘤组织Ca 2+含量明显高于其他组。用放射自显影和western blot研究cAMP和cAMP-H3 BO 3复合物对EGFR自身磷酸化的抑制作用。在体外和在掺入人A549细胞的裸鼠异种移植肺癌模型中研究了新型EGFR抑制剂（cAMP-H3 BO 3复合物）与或不与氧化磷酸化解偶联剂（甲状腺素钠）的抗肿瘤活性。cAMP-H3 BO 3复合物是一种新型的EGFR-TKI。使用cAMP-H3 BO 3与甲状腺素钠诱导的热疗法的联合治疗可能会改善肺癌的治疗结果。
Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. The results suggest that the cAMP-H3BO3 complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro. Compared to the negative control, tumor growth was significantly suppressed in mice treated with oxidative phosphorylation uncoupler thyroxine sodium and either cAMP-H3BO3 complex or cAMP-H3BO3 complex (P < 0.05). Moreover, the body temperature increase induced by treatment with thyroxine sodium inhibited tumor growth. Immunohistochemical analyses showed that A549 cell apoptosis was significantly higher in the cAMP-H3BO3 complex plus thyroxine sodium treatment group than in the other groups. Moreover,Ca2+ content analysis showed that the Ca2+ content of tumor tissue was significantly higher in the cAMP-H3BO3 complex plus thyroxine sodium treatment group than in other groups. Inhibition of EGFR auto-phosphorylation by cAMP and cAMP-H3BO3 complex was studied using autoradiography and western blot. The antitumor activity of the novel EGFR inhibitor (cAMP-H3BO3 complex) with or without an oxidative phosphorylation uncoupler (thyroxine sodium) was investigated in vitro and in a nude mouse xenograft lung cancer model incorporating human A549 cells. cAMP-H3BO3 complex is a novel EGFR-TKI. Combination therapy using cAMP-H3BO3 with thyroxine sodium-induced thermal therapy may improve lung cancer treatment outcomes.