Xihuang pill potentiates the anti-tumor effects of temozolomide in glioblastoma xenografts through the Akt/mTOR-dependent pathway
Copyright © 2020 Elsevier B.V. All rights reserved..
ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill, as a famous traditional Chinese medicine formula, is used for tumor treatment in China. The anti-tumor activities and mechanisms of Xihuang pill still remain unclear.
AIM OF THE STUDY: The Akt/mTOR signaling pathway plays an important role in mediating cell proliferation and apoptosis in glioblastoma. This study aimed to investigate whether Xihuang pill could potentiate temozolomide-induced apoptosis of glioblastoma U87 and U251 cells in vivo and its underlying mechanisms related to Akt/mTOR pathway.
MATERIALS AND METHODS: Human glioblastoma U87 and U251 xenograft models were established. Immunocytochemistry and Western blot were performed to evaluate the anti-proliferative effect, apoptosis and Akt/mTOR signaling mediators.
RESULTS: The results showed that Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone inhibited tumor growth in glioblastoma U87 and U251 xenografts. When Xihuang pill (1 g/kg) and temozolomide (10 mg/kg) were co-administrated, the activities of antitumor growth were markedly increased. Meanwhile, Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone decreased the levels of Ki67 and PCNA expression in glioblastoma U87 and U251 xenografts. In combination treatment group, the inhibitory effects on Ki67 and PCNA expression were significantly enhanced in glioblastoma U87 and U251 xenografts compared to temozolomide treatment alone. Examining the apoptotic index by TUNEL assay showed similar results. Furthermore, Xihuang pill markedly down-regulated the Bcl-2/Bax ratio and inhibited the activation of Akt/mTOR pathway in glioblastoma U87 and U251 xenografts. In addition, no significant signs of toxicities were related to Xihuang pill and/or temozolomide treatment.
CONCLUSIONS: The present study suggested that Xihuang pill might potentiate temozolomide-induced apoptosis of glioblastoma cells in vivo through inhibiting Akt/mTOR-dependent pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:261 |
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| Enthalten in: |
Journal of ethnopharmacology - 261(2020) vom: 28. Okt., Seite 113071 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fu, Jin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.02.2021 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jep.2020.113071 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311816894 |
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| 041 | |a eng | ||
| 100 | 1 | |a Fu, Jin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Xihuang pill potentiates the anti-tumor effects of temozolomide in glioblastoma xenografts through the Akt/mTOR-dependent pathway |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 24.02.2021 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill, as a famous traditional Chinese medicine formula, is used for tumor treatment in China. The anti-tumor activities and mechanisms of Xihuang pill still remain unclear | ||
| 520 | |a AIM OF THE STUDY: The Akt/mTOR signaling pathway plays an important role in mediating cell proliferation and apoptosis in glioblastoma. This study aimed to investigate whether Xihuang pill could potentiate temozolomide-induced apoptosis of glioblastoma U87 and U251 cells in vivo and its underlying mechanisms related to Akt/mTOR pathway | ||
| 520 | |a MATERIALS AND METHODS: Human glioblastoma U87 and U251 xenograft models were established. Immunocytochemistry and Western blot were performed to evaluate the anti-proliferative effect, apoptosis and Akt/mTOR signaling mediators | ||
| 520 | |a RESULTS: The results showed that Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone inhibited tumor growth in glioblastoma U87 and U251 xenografts. When Xihuang pill (1 g/kg) and temozolomide (10 mg/kg) were co-administrated, the activities of antitumor growth were markedly increased. Meanwhile, Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone decreased the levels of Ki67 and PCNA expression in glioblastoma U87 and U251 xenografts. In combination treatment group, the inhibitory effects on Ki67 and PCNA expression were significantly enhanced in glioblastoma U87 and U251 xenografts compared to temozolomide treatment alone. Examining the apoptotic index by TUNEL assay showed similar results. Furthermore, Xihuang pill markedly down-regulated the Bcl-2/Bax ratio and inhibited the activation of Akt/mTOR pathway in glioblastoma U87 and U251 xenografts. In addition, no significant signs of toxicities were related to Xihuang pill and/or temozolomide treatment | ||
| 520 | |a CONCLUSIONS: The present study suggested that Xihuang pill might potentiate temozolomide-induced apoptosis of glioblastoma cells in vivo through inhibiting Akt/mTOR-dependent pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Akt | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Temozolomide | |
| 650 | 4 | |a Xihuang pill | |
| 650 | 4 | |a mTOR | |
| 650 | 7 | |a Antineoplastic Agents, Alkylating |2 NLM | |
| 650 | 7 | |a BAX protein, human |2 NLM | |
| 650 | 7 | |a BCL2 protein, human |2 NLM | |
| 650 | 7 | |a Drugs, Chinese Herbal |2 NLM | |
| 650 | 7 | |a Ki-67 Antigen |2 NLM | |
| 650 | 7 | |a MKI67 protein, human |2 NLM | |
| 650 | 7 | |a PCNA protein, human |2 NLM | |
| 650 | 7 | |a Proliferating Cell Nuclear Antigen |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-bcl-2 |2 NLM | |
| 650 | 7 | |a bcl-2-Associated X Protein |2 NLM | |
| 650 | 7 | |a xihuang |2 NLM | |
| 650 | 7 | |a MTOR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.1.1 |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Temozolomide |2 NLM | |
| 650 | 7 | |a YF1K15M17Y |2 NLM | |
| 700 | 1 | |a Zhu, Shi-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Hong-Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, You-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Ping-Shi |e verfasserin |4 aut | |
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