Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
Abstract Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS),...
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Nature Portfolio
2023-12-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-023-48777-z |
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author | Songxian Zhu Jingjing Guo Li Yu Jun Liu Jixiang Chen Jinxin Xin Yuqiang Zhang Jie Luo Chao Duan |
author_facet | Songxian Zhu Jingjing Guo Li Yu Jun Liu Jixiang Chen Jinxin Xin Yuqiang Zhang Jie Luo Chao Duan |
author_sort | Songxian Zhu |
collection | DOAJ |
description | Abstract Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 μM CTS and 200 μM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs’ synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy. |
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last_indexed | 2024-03-09T01:19:53Z |
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spelling | doaj.art-c85a6a1ff25c486e91fbad9f5d7bae932023-12-10T12:15:10ZengNature PortfolioScientific Reports2045-23222023-12-0113111010.1038/s41598-023-48777-zSynergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cellsSongxian Zhu0Jingjing Guo1Li Yu2Jun Liu3Jixiang Chen4Jinxin Xin5Yuqiang Zhang6Jie Luo7Chao Duan8Brain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineMedical Services, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineAbstract Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 μM CTS and 200 μM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs’ synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy.https://doi.org/10.1038/s41598-023-48777-z |
spellingShingle | Songxian Zhu Jingjing Guo Li Yu Jun Liu Jixiang Chen Jinxin Xin Yuqiang Zhang Jie Luo Chao Duan Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells Scientific Reports |
title | Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells |
title_full | Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells |
title_fullStr | Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells |
title_full_unstemmed | Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells |
title_short | Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells |
title_sort | synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells |
url | https://doi.org/10.1038/s41598-023-48777-z |
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