Tong Yongpeng, Huang Chunliu, Zhang Junfang
College of Physics and Energy, Shenzhen University, Shenzhen, 518060, China.
School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
Oncotarget. 2017 May 5;8(34):56327-56337. doi: 10.18632/oncotarget.17628. eCollection 2017 Aug 22.
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-HBO complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest . Compared to the negative control, tumor growth was significantly suppressed in mice treated with oxidative phosphorylation uncoupler thyroxine sodium and either cAMP-HBO complex or cAMP-HBO complex ( < 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-HBO complex plus thyroxine sodium treatment group than in the other groups. Moreover,Ca content analysis showed that the Ca content of tumor tissue was significantly higher in the cAMP-HBO complex plus thyroxine sodium treatment group than in other groups.
Inhibition of EGFR auto-phosphorylation by cAMP and cAMP-HBO complex was studied using autoradiography and western blot. The antitumor activity of the novel EGFR inhibitor (cAMP-HBO complex) with or without an oxidative phosphorylation uncoupler (thyroxine sodium) was investigated and in a nude mouse xenograft lung cancer model incorporating human A549 cells.
cAMP-HBO complex is a novel EGFR-TKI. Combination therapy using cAMP-HBO with thyroxine sodium-induced thermal therapy may improve lung cancer treatment outcomes.
尽管表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）作为一线非小细胞肺癌治疗药物能产生良好疗效，但耐药性仍是一个严重问题。同时，热疗法也显示出作为一种癌症治疗策略的前景。在此，我们将一种新型EGFR-TKI治疗与热疗法相结合，以改善肺癌治疗效果。
结果表明，环磷酸腺苷-高压氧（cAMP-HBO）复合物能有效抑制表皮生长因子受体（EGFR）的自身磷酸化，同时诱导细胞凋亡和细胞周期停滞。与阴性对照组相比，用氧化磷酸化解偶联剂甲状腺素钠和cAMP-HBO复合物或cAMP-HBO复合物处理的小鼠肿瘤生长受到显著抑制（<0.05）。此外，甲状腺素钠处理引起的体温升高抑制了肿瘤生长。免疫组织化学分析表明，cAMP-HBO复合物加甲状腺素钠处理组的A549细胞凋亡明显高于其他组。此外，钙含量分析表明，cAMP-HBO复合物加甲状腺素钠处理组肿瘤组织的钙含量明显高于其他组。
采用放射自显影和蛋白质印迹法研究cAMP和cAMP-HBO复合物对EGFR自身磷酸化的抑制作用。在一个包含人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-HBO复合物）在有或没有氧化磷酸化解偶联剂（甲状腺素钠）情况下的抗肿瘤活性。
cAMP-HBO复合物是一种新型EGFR-TKI。cAMP-HBO与甲状腺素钠诱导的热疗法联合治疗可能改善肺癌治疗效果。
