Gallic acid enhances the antitumor activity of Icotinib hydrochloride in non-small cell lung cancer via of Hippo-YAP signaling pathway in vitro and in vivo

Abstract

Icotinib hydrochloride (IH) is a small molecular TKI independently developed in China. As the first-line anti-tumor agent, is widely used for treatment of non-small cell lung cancer (NSCLC). Gallic acid (GA), a natural plant extract, is reported that it has a variety of pharmacological and biological properties. GA is a active natural phenolic extracted from Tannins that has been shown to exhibit anticancer activities on various types of tumors. Here, we reported that GA was capable of sensitizing A549/PC9 cells to IH by enhancing apoptosis. Mechanistic analyses indicated that IH-induced caspase-3-dependent apoptosis was elevated in the presence of GA through activating extracellular signal-regulated Hippo-YAP pathway. Furthermore, GA also promoted IH-induced cytotoxic, downregulated expression of p-YAP and caspase-3. In vivo, the co-treatment of IH and GA notably reduced the tumor size when compared with IH treatment alone. Notably, GA significantly reduced the toxicity generated by IH in tumor-bearing mice. This study identifies the unique role of GA enhance IH sensitivity through apoptosis, and suggests that combined IH and GA might be a novel therapeutic strategy for patients with NSCLC.