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

doi:10.2147/OTT.S432901

Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway

Onco Targets Ther. 2023 Nov 22:16:983-994. doi: 10.2147/OTT.S432901. eCollection 2023.

Authors

Zi-Qi Li^#¹, Guo-Song Zhang^#¹, Ri-Qun Liu¹, Shu-Yuan Shuai¹, Peng-Yi Hu¹, Qin Zheng¹, Shu-Hua Xiao¹

Affiliation

¹ Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, 330004, People's Republic of China.

^# Contributed equally.

Abstract

Background: 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: PI3K/Akt signaling pathway; glioma; ligustilide; n-butylphthalide; synergistic effect.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 82060719), the Chinese Medicine Preparation Technology and Equipment Innovation Team of the Jiangxi University of Chinese Medicine (NO.CXTD22006) and the Innovation and Entrepreneurship Project for College Students (NO.X202310412138).