Dezocine induces apoptosis in human cervical carcinoma Hela cells via the endoplasmic reticulum stress pathway

Wang，Hanlin1,2; Chiang，Chengyao3; Xue，Chenyang1; Zhou，Lu4; Li，Shuaihu1; Zhou，Yaqi5; Zhang，Zhucheng1; Xie，Meng1; Xiao，Tian1; Hu，Hongyi5; Zhu，Lizhi6; Long，Cheng2; Zou，Yongdong1; Wang，Ting2; Zheng，Duo1

2022-06-01

10.1093/toxres/tfac026

Toxicology Research   影响因子和分区

2045-452X

2045-4538

Dezocine, a dual agonist and antagonist of the μ-opioid receptor and κ-opioid receptor, is widely used as an analgesic in China. At present, there are few studies on anti-tumor effects of dezocine, most of which are used to treat cancer pain. However, it has recently been reported that dezocine can induce apoptosis of triple negative breast cancer cells. Dezocine may have some anti-tumor activity, but the effect and potential mechanism of dezocine in the treatment of other types of cancer remain to be fully studied. The purpose of the present study was to investigate the effect of dezocine on human Hela cervical carcinoma cells, and to elucidate the underlying molecular mechanisms. We performed CCK-8 assays, clone formation assays, xenograft, flow cytometry analysis, western blot and RNA-seq analysis to evaluate the effects of dezocine on Hela cells. In addition, the role of endoplasmic reticulum (ER) stress in dezocine-induced apoptosis was investigated using qPCR and western blot analysis. Dezocine inhibited Hela cell viability in dose-dependent and time-dependent manners, and notably did not achieve this effect by targeting the opioid receptors. Further mechanistic studies demonstrated that dezocine activated ER stress by upregulating the expression of GRP78, IRE1 and p-JNK, and that dezocine-induced apoptosis was attenuated when the ER stress pathway was blocked. Our results provide a foundation to support the redefinition of dezocine as a novel, adjuvant treatment for patients with cervical cancer, although further research will be required to support its application in clinical practice.

apoptosis cervical cancer dezocine ER stress opioid receptor

SCI

英语

其他

WOS:000805234900001

2-s2.0-85134357883

Scopus

1.Department of Cell Biology and Genetics,College of Life Sciences and Oceanography,Shenzhen University,Shenzhen,518055,China
2.Institute for Brain Research and Rehabilitation,South China Normal University,Guangzhou,510631,China
3.Central Laboratory,Southern University of Science and Technology Yantian Hospital,Shenzhen,518081,China
4.Southern Medical University,Maternal and Child Healthcare Hospital of Shenzhen City,Shenzhen,518028,China
5.Department of Otolaryngology,Peking University Shenzhen Hospital,Shenzhen,518036,China
6.First Affiliated Hospital of Shenzhen University,Shenzhen Second People's Hospital,institute of Translation Medicine,Shenzhen,518035,China

Wang，Hanlin,Chiang，Chengyao,Xue，Chenyang,et al. Dezocine induces apoptosis in human cervical carcinoma Hela cells via the endoplasmic reticulum stress pathway[J]. Toxicology Research,2022,11(3):498-510.

Wang，Hanlin.,Chiang，Chengyao.,Xue，Chenyang.,Zhou，Lu.,Li，Shuaihu.,...&Zheng，Duo.(2022).Dezocine induces apoptosis in human cervical carcinoma Hela cells via the endoplasmic reticulum stress pathway.Toxicology Research,11(3),498-510.

Wang，Hanlin,et al."Dezocine induces apoptosis in human cervical carcinoma Hela cells via the endoplasmic reticulum stress pathway".Toxicology Research 11.3(2022):498-510.