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

// Yongpeng Tong 1 , Chunliu Huang 2 and Junfang Zhang 3 1 College of Physics and Energy, Shenzhen University, Shenzhen, 518060, China 2 School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China 3 School of Medicine, Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518060, China Correspondence to: Junfang Zhang, email: junfang.zhang@163.com Keywords: cAMP-H 3 BO 3 complex, EGFR-TKI, thermal therapy, NSCLC Received: February 01, 2017      Accepted: April 21, 2017      Published: May 05, 2017 ABSTRACT Purpose: 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. Results: The results suggest that the cAMP-H 3 BO 3 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-H 3 BO 3 complex or cAMP-H 3 BO 3 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-H 3 BO 3 complex plus thyroxine sodium treatment group than in the other groups. Moreover,Ca 2+ content analysis showed that the Ca 2+ content of tumor tissue was significantly higher in the cAMP-H 3 BO 3 complex plus thyroxine sodium treatment group than in other groups. Materials and Methods: Inhibition of EGFR auto-phosphorylation by cAMP and cAMP-H 3 BO 3 complex was studied using autoradiography and western blot. The antitumor activity of the novel EGFR inhibitor (cAMP-H 3 BO 3 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. Conclusions: cAMP-H 3 BO 3 complex is a novel EGFR-TKI. Combination therapy using cAMP-H 3 BO 3 with thyroxine sodium-induced thermal therapy may improve lung cancer treatment outcomes.