Research Papers:

Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking β1 integrin activation

Li-Yan Li _, Hong Jiang, Yang-Min Xie, Lian-Di Liao, Hui-Hui Cao, Xiu-E Xu, Bo Chen, Fa-Min Zeng, Ying-Li Zhang, Ze-Peng Du, Hong Chen, Wei Huang, Wei Jia, Wei Zheng, Jian-Jun Xie, En-Min Li and Li-Yan Xu

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Oncotarget. 2015; 6:15940-15952. https://doi.org/10.18632/oncotarget.3612

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Li-Yan Li1,2,*, Hong Jiang3,*, Yang-Min Xie4, Lian-Di Liao1,2, Hui-Hui Cao1,2, Xiu-E Xu1,2, Bo Chen1,2, Fa-Min Zeng1,5, Ying-Li Zhang1,2, Ze-Peng Du1,2, Hong Chen3, Wei Huang3, Wei Jia3, Wei Zheng3, Jian-Jun Xie1,5, En-Min Li1,5, Li-Yan Xu1,2

1The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China

2Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China

3Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, Fujian, P.R. China

4Experimental Animal Center, Shantou University Medical College, Shantou, Guangdong, P.R. China

5Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Li-Yan Xu, e-mail: [email protected]

En-Min Li, e-mail: [email protected]

Keywords: macrolide analog F806, β1 integrin, cell adhesion, anoikis, esophageal squamous cell carcinoma cells

Received: January 21, 2015     Accepted: March 14, 2015     Published: April 03, 2015


The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC50) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.

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