IL-6 derived from therapy-induced senescence facilitates the glycolytic phenotype in glioblastoma cells

Gu, Jiayu1,2,3; Wang, Jingyi1; Liu, Xincheng1; Sai, Ke4,5; Mai, Jialuo1; Xing, Fan1; Chen, Zhijie4; Yang, Xiaozhi1; Lu, Wanjun1; Guo, Cui1; Liu, Wenfeng1; Xu, Yang1; Xie, Shouxia2,3; Hu, Cheng1; Yen, Guangmei1; Zhu, Wenbo1

2021

American Journal of Cancer Research   影响因子和分区

2156-6976

Activation of the cyclic adenosine monophosphate (cAMP) pathway induces the glial differentiation of glioblastoma (GBM) cells, but the fate of differentiated cells remains poorly understood. Transcriptome analyses have revealed significant changes in the cell cycle- and senescence-related pathways in differentiated GBM cells induced by dibutyryl cAMP (dbcAMP). Further investigations showed that reactive oxygen species (ROS) derived from enhanced mitochondrial function are involved in senescence induction and proliferation inhibition. Moreover, we found that IL-6 from dbcAMP- or temozolomide (TMZ)-induced senescent cells facilitates the glycolytic phenotype of GBM cells and that inhibiting the IL-6-related pathway hinders the proglycolytic effect of either agent. In patient-derived GBM xenograft models, a specific antibody targeting the IL-6 receptor tocilizumab (TCZ) significantly prolongs the survival time of TMZ-treated mice. Taken together, these results suggest that both the differentiation-inducing agent dbcAMP and the chemotherapy drug TMZ are able to drive GBM cells to senescence, and the latter releases IL-6 to potentiate glycolysis, suggesting that IL-6 is a target for adjuvant chemotherapy in GBM treatment.

Glioblastoma senescence IL-6 glycolysis

SCI

英语

其他

National Natural Science Foundation of China[81872886,"81872-887",81802536,81773751] ; Natural Science Foundation of Guangdong Province[2017A030313620] ; National Major Scientific, Technological Special Project for "Significant New Drugs Development" during the 13th Five-Year Plan Period[2018ZXO9733-002] ; Pioneering talents project of Guangzhou Development Zone, Guangdong Province[CY2018-012] ; Shenzhen Key Medical Discipline Construction Fund[SZXK059]

Oncology

Oncology

WOS:000614152500009

E-CENTURY PUBLISHING CORP

Web of Science

1.Sun Yat Sen Univ, Dept Pharmacol, Zhongshan Sch Med, 74 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China
2.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Pharm, Jinan, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Peoples R China
4.Sun Yat Sen Univ, Canc Ctr, Dept Neurosurg Neurooncol, Guangzhou, Peoples R China
5.Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou, Peoples R China

Gu, Jiayu,Wang, Jingyi,Liu, Xincheng,et al. IL-6 derived from therapy-induced senescence facilitates the glycolytic phenotype in glioblastoma cells[J]. American Journal of Cancer Research,2021,11(2).

Gu, Jiayu.,Wang, Jingyi.,Liu, Xincheng.,Sai, Ke.,Mai, Jialuo.,...&Zhu, Wenbo.(2021).IL-6 derived from therapy-induced senescence facilitates the glycolytic phenotype in glioblastoma cells.American Journal of Cancer Research,11(2).

Gu, Jiayu,et al."IL-6 derived from therapy-induced senescence facilitates the glycolytic phenotype in glioblastoma cells".American Journal of Cancer Research 11.2(2021).