机构：[1]Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China[2]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, #1055 Sanxiang Road, Suzhou, Jiangsu, China[3]Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China
ObjectiveMalignant glioma is a lethal brain tumor with a low survival rate and poor prognosis. New strategies are urgently needed to augment the chemotherapeutic effects of temozolomide (TMZ), the standard drug in glioma treatment. Carnosic acid (CA) has been reported to have anticancer, antioxidant and anti-infectious properties. In this study, we aimed to investigate the anticancer effects and the underlying mechanisms of CA in combination with TMZ in glioma cancer cells.MethodsThe glioma cancer cells were treated with TMZ, CA, or TMZ+CA. We evaluated cell survival by CCK-8 assay, cell anchorage-independent survival by colony formation assay, cell migration by wound-healing assay, cell cycle and cell apoptosis by flow cytometry, and protein expression by western blot.ResultsCA enhanced the cytotoxic effect of TMZ in glioma cancer cells. CA enhanced TMZ-induced inhibition of colony formation and cell migration and enhanced TMZ-induced cell cycle arrest and cellular apoptosis. Immunofluorescence suggested that CA in combination with TMZ triggered autophagy. Furthermore, CA promoted TMZ-induced cell cycle arrest and cellular apoptosis by Cyclin B1 inhibition and activation of PARP and Caspase-3, while CA promoted TMZ-induced cellular autophagy by p-AKT inhibition, p62 downregulation and LC3-I to LC3-II transition.ConclusionThese data suggest that the combination therapy of CA and TMZ strengthens the anticancer effect of TMZ by enhancing apoptosis and autophagy.
基金：
This study was funded by the National Natural Science Foundation
of China (81302197), the Changzhou Science and Technology
Support Program (CE20165048), the Changzhou High-Level Medical
Talents Training Project (2016CZBJ006), and the Changzhou Municipal
Commissions of Health and Family Planning Major Scientific and
Technological Project (ZD201620).
第一作者机构：[1]Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China[2]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, #1055 Sanxiang Road, Suzhou, Jiangsu, China
通讯作者：
通讯机构：[1]Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China[2]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, #1055 Sanxiang Road, Suzhou, Jiangsu, China[3]Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China
推荐引用方式(GB/T 7714)：
Naiyuan Shao,Jiahao Mao,Lian Xue,et al.Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma[J].JOURNAL OF NEURO-ONCOLOGY.2019,141(2):277-288.doi:10.1007/s11060-018-03043-5.
APA：
Naiyuan Shao,Jiahao Mao,Lian Xue,Rong Wang,Feng Zhi&Qing Lan.(2019).Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma.JOURNAL OF NEURO-ONCOLOGY,141,(2)
MLA：
Naiyuan Shao,et al."Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma".JOURNAL OF NEURO-ONCOLOGY 141..2(2019):277-288
