Oncotarget

Research Papers:

A novel EGFR-TKI inhibitor (cAMP-H3BO3 complex) combined with thermal therapy is a promising strategy to improve lung cancer treatment outcomes

Yongpeng Tong, Chunliu Huang and Junfang Zhang _

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Oncotarget. 2017; 8:56327-56337. https://doi.org/10.18632/oncotarget.17628

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Abstract

Yongpeng Tong1, Chunliu Huang2 and Junfang Zhang3

1College of Physics and Energy, Shenzhen University, Shenzhen, 518060, China

2School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China

3School of Medicine, Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518060, China

Correspondence to:

Junfang Zhang, email: [email protected]

Keywords: cAMP-H3BO3 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-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.

Materials and Methods: 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.

Conclusions: 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.


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