Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway
Zi-Qi Li,* Guo-Song Zhang,* Ri-Qun Liu, Shu-Yuan Shuai, Peng-Yi Hu, Qin Zheng, Shu-Hua Xiao Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China*These...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2023-11-01
|
| Series: | OncoTargets and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/anti-glioma-effects-of-ligustilide-or-n-butylphthalide-on-their-own-an-peer-reviewed-fulltext-article-OTT |
| _version_ | 1797486275878453248 |
|---|---|
| author | Li ZQ Zhang GS Liu RQ Shuai SY Hu PY Zheng Q Xiao SH |
| author_facet | Li ZQ Zhang GS Liu RQ Shuai SY Hu PY Zheng Q Xiao SH |
| author_sort | Li ZQ |
| collection | DOAJ |
| description | Zi-Qi Li,* Guo-Song Zhang,* Ri-Qun Liu, Shu-Yuan Shuai, Peng-Yi Hu, Qin Zheng, Shu-Hua Xiao Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Yi Hu; Qin Zheng, Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China, Tel/Fax +86 0791 87118658, Email hpy820515@126.com; zhengqin912006@163.comBackground: Ligustilide (LIG) and n-butylphthalide (NBP) have neuroprotective effects in cerebral ischemia; however, their roles in gliomas are not well-known.This study aimed to explore the anti-glioma effects of LIG and NBP individually and the synergistic effects of temozolomide (TMZ) via the PI3K/Akt Signaling Pathway.Materials and Methods: Cytotoxicity of LIG and NBP alone and in combination with TMZ in U251 cells was determined using the CCk-8. The effect of compounds alone or in combination on cell migration was detected using the wound healing assay, and the invasion was evaluated by transwell assays, respectively. Cell apoptosis was quantified by flow cytometry and the changed expressions of proteins were detected by Western blotting.Results: The results showed that LIG and NBP significantly inhibited the growth of U251 cells at concentrations of 4– 10 μg/mL and 1.5– 6 μg/mL in a dose-dependent manner (p< 0.05, p< 0.01). The combination of 20 μg/mL TMZ with LIG in the concentration range of 4– 10 μg/mL or with NBP of 0.5– 6 μg/mlachieved synergistic effect towardsU251 cells. LIG and NBP, alone or in combination with TMZ, markedly inhibited cell invasion (p< 0.001) and enhanced apoptosis (p< 0.05). The combination of TMZ with LIG or NBP markedly inhibited cell migration (p< 0.001). Western blot analysis showed that LIG, NBP, and TMZ, alone and in combination, significantly decreased the expression of Bcl-2, p-PI3K, and p-Akt, and increased the expression of Bax.Conclusion: Both LIG and NBP exert anti-glioma effects on their own through the PI3K/Akt pathway and enhance TMZ-mediated anti-glioma efficiency via the same pathway. Keywords: ligustilide, n-butylphthalide, glioma, synergistic effect, PI3K/Akt signaling pathway |
| first_indexed | 2024-03-09T23:31:52Z |
| format | Article |
| id | doaj.art-1d01377d6f904eceb3cd8cc5c1971eba |
| institution | Directory Open Access Journal |
| issn | 1178-6930 |
| language | English |
| last_indexed | 2024-03-09T23:31:52Z |
| publishDate | 2023-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | OncoTargets and Therapy |
| spelling | doaj.art-1d01377d6f904eceb3cd8cc5c1971eba2023-11-23T17:07:56ZengDove Medical PressOncoTargets and Therapy1178-69302023-11-01Volume 1698399488430Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling PathwayLi ZQZhang GSLiu RQShuai SYHu PYZheng QXiao SHZi-Qi Li,* Guo-Song Zhang,* Ri-Qun Liu, Shu-Yuan Shuai, Peng-Yi Hu, Qin Zheng, Shu-Hua Xiao Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Yi Hu; Qin Zheng, Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China, Tel/Fax +86 0791 87118658, Email hpy820515@126.com; zhengqin912006@163.comBackground: Ligustilide (LIG) and n-butylphthalide (NBP) have neuroprotective effects in cerebral ischemia; however, their roles in gliomas are not well-known.This study aimed to explore the anti-glioma effects of LIG and NBP individually and the synergistic effects of temozolomide (TMZ) via the PI3K/Akt Signaling Pathway.Materials and Methods: Cytotoxicity of LIG and NBP alone and in combination with TMZ in U251 cells was determined using the CCk-8. The effect of compounds alone or in combination on cell migration was detected using the wound healing assay, and the invasion was evaluated by transwell assays, respectively. Cell apoptosis was quantified by flow cytometry and the changed expressions of proteins were detected by Western blotting.Results: The results showed that LIG and NBP significantly inhibited the growth of U251 cells at concentrations of 4– 10 μg/mL and 1.5– 6 μg/mL in a dose-dependent manner (p< 0.05, p< 0.01). The combination of 20 μg/mL TMZ with LIG in the concentration range of 4– 10 μg/mL or with NBP of 0.5– 6 μg/mlachieved synergistic effect towardsU251 cells. LIG and NBP, alone or in combination with TMZ, markedly inhibited cell invasion (p< 0.001) and enhanced apoptosis (p< 0.05). The combination of TMZ with LIG or NBP markedly inhibited cell migration (p< 0.001). Western blot analysis showed that LIG, NBP, and TMZ, alone and in combination, significantly decreased the expression of Bcl-2, p-PI3K, and p-Akt, and increased the expression of Bax.Conclusion: Both LIG and NBP exert anti-glioma effects on their own through the PI3K/Akt pathway and enhance TMZ-mediated anti-glioma efficiency via the same pathway. Keywords: ligustilide, n-butylphthalide, glioma, synergistic effect, PI3K/Akt signaling pathwayhttps://www.dovepress.com/anti-glioma-effects-of-ligustilide-or-n-butylphthalide-on-their-own-an-peer-reviewed-fulltext-article-OTTligustiliden-butylphthalidegliomasynergistic effectpi3k/akt signaling pathway |
| spellingShingle | Li ZQ Zhang GS Liu RQ Shuai SY Hu PY Zheng Q Xiao SH Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway OncoTargets and Therapy ligustilide n-butylphthalide glioma synergistic effect pi3k/akt signaling pathway |
| title | Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway |
| title_full | Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway |
| title_fullStr | Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway |
| title_full_unstemmed | Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway |
| title_short | Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway |
| title_sort | anti glioma effects of ligustilide or n butylphthalide on their own and the synergistic effects with temozolomide via pi3k akt signaling pathway |
| topic | ligustilide n-butylphthalide glioma synergistic effect pi3k/akt signaling pathway |
| url | https://www.dovepress.com/anti-glioma-effects-of-ligustilide-or-n-butylphthalide-on-their-own-an-peer-reviewed-fulltext-article-OTT |
| work_keys_str_mv | AT lizq antigliomaeffectsofligustilideornbutylphthalideontheirownandthesynergisticeffectswithtemozolomideviapi3kaktsignalingpathway AT zhanggs antigliomaeffectsofligustilideornbutylphthalideontheirownandthesynergisticeffectswithtemozolomideviapi3kaktsignalingpathway AT liurq antigliomaeffectsofligustilideornbutylphthalideontheirownandthesynergisticeffectswithtemozolomideviapi3kaktsignalingpathway AT shuaisy antigliomaeffectsofligustilideornbutylphthalideontheirownandthesynergisticeffectswithtemozolomideviapi3kaktsignalingpathway AT hupy antigliomaeffectsofligustilideornbutylphthalideontheirownandthesynergisticeffectswithtemozolomideviapi3kaktsignalingpathway AT zhengq antigliomaeffectsofligustilideornbutylphthalideontheirownandthesynergisticeffectswithtemozolomideviapi3kaktsignalingpathway AT xiaosh antigliomaeffectsofligustilideornbutylphthalideontheirownandthesynergisticeffectswithtemozolomideviapi3kaktsignalingpathway |