DHA increases the anti-tumor effect of gefitinib on non-small cell lung cancer with EGFR mutations in vitro
作者
Ren, WG;Wu, J;Wang, XH;Feng, Z;Shang, XC;Peng, ZM
作者单位
[Ren, Wangang; Wang, Xiaohang; Feng, Zhen; Peng, Zhongmin] Shandong Univ, Shandong Prov Hosp, Dept Thorac Surg, 9677 Jing 10 Rd, Jinan 250000, Shandong, Peoples R China.;-;[Wu, Jing] Shandong Univ, Shandong Prov Hosp, Dept Operat, Jinan, Shandong, Peoples R China.;-;[Shang, Xingchen] Shandong Univ, Shandong Prov Hosp, Dept Breast & Thyroid Surg, Jinan, Shandong, Peoples R China.
摘要
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved as first-line therapy for patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. Docosahexaenoic acid (DHA) exerts anti-neoplastic activity in human lung cancer cells. In this study, we investigated whether DHA increases the anti-tumor effects of gefitinib on NSCLC cells with EGFR mutations and the related mechanisms of action. We determined the effects of DHA and gefitinib on the proliferation, apoptosis, cell cycle, and signaling pathways of NSCLC cells with EGFR activating mutations (PC9 cells) and TKI resistance (A549 cells). DHA had an obvious inhibitory effect on both cell lines, and enhanced the anti-tumor effects of gefitinib on the cells in vitro. Combined gefitinib and DHA therapy had a synergistic effect, inducing apoptosis, causing G0/G1 arrest in the PC9 cells and affecting EGFR and ERK1/2 signaling. These results suggest that DHA can act as a sensitizer of gefitinib in NSCLC cells with EGFR mutations. Nutritional intervention with DHA is a promising approach to enhancing the therapeutic effect of gefitinib.
关键词
POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; GROWTH; CHEMOTHERAPY; EXPRESSION; CONSUMPTION; APOPTOSIS; PATHWAYS; THERAPY; DISEASE
基本信息
