J Cancer 2019; 10(26):6543-6556. doi:10.7150/jca.34285

Research Paper

Synergistic inhibition of lung cancer cells by EGCG and NF-κB inhibitor BAY11-7082

Lingyu Zhang1, Jing Xie2,3, Ruihuan Gan2,3, Zhangwei Wu4, Huatian Luo4, Xingyong Chen4, Youguang Lu2,3, Lixian Wu1✉, Dali Zheng3✉

1. School of Pharmacy, Fujian Medical University, 1 Xueyuan Road, University Town, Fuzhou, 350122, China.
2. Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, 246 Middle Yangqiao Road, Fuzhou, 350001, China.
3. Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Rd, Fuzhou, 350004, China.
4. Shengli Clinical Collage, Fujian Medical University, 134 East Street, Fuzhou, 350001, China.

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Citation:
Zhang L, Xie J, Gan R, Wu Z, Luo H, Chen X, Lu Y, Wu L, Zheng D. Synergistic inhibition of lung cancer cells by EGCG and NF-κB inhibitor BAY11-7082. J Cancer 2019; 10(26):6543-6556. doi:10.7150/jca.34285. Available from http://www.jcancer.org/v10p6543.htm

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Abstract

Lung cancer has a poor 5-year survival rate and is the leading cause of cancer-related deaths worldwide. Thus, the development of more efficient therapeutic strategies is urgently needed. Many studies have shown that EGCG, a major polyphenol found in green tea, has potential anticancer effects. The present study aims to investigate the molecular mechanism of EGCG-mediated inhibition of proliferation in lung cancer cells and to explore the effects of combined treatment with EGCG and an NF-κB inhibitor, BAY11-7082, in A549 and H1299 cells both in vitro and in vivo. Our results showed that EGCG inhibits cell proliferation and migration and induces apoptosis in A549 and H1299 cells at relatively high concentrations (IC50=86.4 µM for A549 cells and 80.6 µM for H1299 cells). These effects are partially achieved via inhibition of the NF-κB signaling pathway. Combined treatment with EGCG and BAY11-7082, a potent NF-κB inhibitor, shows significant synergistic effects at relatively low concentrations. The inhibition rate reached approximately 50% in cells treated for 72 h with 20 µM EGCG and 5 µM (A549 cells) or 2.5 µM BAY11-7082 (H1299 cells). This synergistic anti-tumor effect was also observed in a xenograft model. These results indicated that EGCG inhibits lung cancer cell proliferation by suppressing NF-κB signaling. Coadministration of EGCG and BAY11-7082 has a synergistic effect both in vitro and in vivo and may serve as a novel therapeutic strategy for lung cancer.

Keywords: EGCG, BAY11-7082, NF-κB, Apoptosis