Sequential treatment with AT-101 enhances cisplatin chemosensitivity in human non-small cell lung cancer cells through inhibition of apurinic/apyrimidinic endonuclease 1-activated IL-6/STAT3 signaling pathway.
机构：[1]Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of China[2]Oncology Department, The Affiliated Hospital, North Sichuan Medical College, Nanchong, People’s Republic of China[3]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA
AT-101, known as R-(-)-gossypol, is a potent anticancer agent, but its chemosensitizing effects remain elusive. The present study aimed to examine whether AT-101 could increase the sensitivity of non-small cell lung cancer A549 cells to cisplatin (CDDP) and the underlying mechanisms. We evaluated the efficacy of the sequential treatment with AT-101 and CDDP using both in vitro and in vivo models. Our results showed that as compared to AT-101 or CDDP monotherapy, or AT-101 plus CDDP concurrent treatment, the sequential treatment significantly inhibited cell proliferation and migration and induced tumor cell death. Moreover, the efficacy of the sequential treatment was also confirmed in a mouse A549 xenograft model. Our study revealed that AT-101 inhibited the reduced status of apurinic/apyrimidinic endonuclease 1 (APE1) and attenuated APE1-mediated IL-6/STAT3 signaling activation by decreasing IL-6 protein expression; suppressing the STAT3-DNA binding; and reducing the expression of the downstream antiapoptotic proteins Bcl-2 and Bcl-xL. In conclusion, AT-101 enhances the sensitivity of A549 cells to CDDP in vitro and in vivo through the inhibition of APE1-mediated IL-6/STAT3 signaling activation, providing a rationale for the combined use of AT-101 and CDDP in non-small cell lung cancer chemotherapy.
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外文
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出版当年[2014]版：
大类|3 区医学
小类|3 区药物化学3 区药学
最新[2023]版：
大类|2 区医学
小类|2 区药物化学2 区药学
第一作者：
第一作者机构：[1]Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of China[2]Oncology Department, The Affiliated Hospital, North Sichuan Medical College, Nanchong, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of China[*1]Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, No 10 Changjiang Zhi Road, Yuzhong District, Chongqing 400042, People’s Republic of China
推荐引用方式(GB/T 7714)：
Tao Ren,Jinlu Shan,Yi Qing,et al.Sequential treatment with AT-101 enhances cisplatin chemosensitivity in human non-small cell lung cancer cells through inhibition of apurinic/apyrimidinic endonuclease 1-activated IL-6/STAT3 signaling pathway.[J].Drug design, development and therapy.2014,8:2517-29.doi:10.2147/DDDT.S71432.
APA：
Tao Ren,Jinlu Shan,Yi Qing,Chengyuan Qian,Qing Li...&Shu-Feng Zhou.(2014).Sequential treatment with AT-101 enhances cisplatin chemosensitivity in human non-small cell lung cancer cells through inhibition of apurinic/apyrimidinic endonuclease 1-activated IL-6/STAT3 signaling pathway..Drug design, development and therapy,8,
MLA：
Tao Ren,et al."Sequential treatment with AT-101 enhances cisplatin chemosensitivity in human non-small cell lung cancer cells through inhibition of apurinic/apyrimidinic endonuclease 1-activated IL-6/STAT3 signaling pathway.".Drug design, development and therapy 8.(2014):2517-29
