2. Academic Validation
  3. Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking β1 integrin activation

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

  • Oncotarget. 2015 Jun 30;6(18):15940-52. doi: 10.18632/oncotarget.3612.
Li-Yan Li 1 2,  Hong Jiang 3,  Yang-Min Xie 4,  Lian-Di Liao 1 2,  Hui-Hui Cao 1 2,  Xiu-E Xu 1 2,  Bo Chen 1 2,  Fa-Min Zeng 1 5,  Ying-Li Zhang 1 2,  Ze-Peng Du 1 2,  Hong Chen 3,  Wei Huang 3,  Wei Jia 3,  Wei Zheng 3,  Jian-Jun Xie 1 5,  En-Min Li 1 5,  Li-Yan Xu 1 2
Affiliations

Affiliations

  • 1 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, P.R. China.
  • 2 Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
  • 3 Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, Fujian, P.R. China.
  • 4 Experimental Animal Center, Shantou University Medical College, Shantou, Guangdong, P.R. China.
  • 5 Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, P.R. China.
PMID: 25909284 DOI: 10.18632/oncotarget.3612
Abstract

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.

Keywords

anoikis; cell adhesion; esophageal squamous cell carcinoma cells; macrolide analog F806; β1 integrin.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z