Details

Autor(en) / Beteiligte

• Wang, Xinzhuang
• Ye, Junyi
• Gao, Ming
• Zhang, Dongzhi
• Jiang, Haiping
• Zhang, Hong
• Zhao, Shiguang
• Liu, Xianzhi

Titel

Nifuroxazide inhibits the growth of glioblastoma and promotes the infiltration of CD8 T cells to enhance antitumour immunity

Ist Teil von

• International immunopharmacology, 2023-05, Vol.118, p.109987-109987, Article 109987

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• nifuroxazide can inhibit the proliferation of glioblastoma cells, promote G2 phase arrest, induce apoptosis, and inhibit epithelial-mesenchymal transition through the MAP3K1/JAK2/STAT3 pathway. Similarly, clinical sample analysis confirmed that MAP3K1 combined with STAT3 can affect the prognostic characteristics of patients with glioma. In addition, nifuroxazide can drive the M1 polarization of microglioma cells, inhibit the expression of CTLA4 and PD-L1 in tumour cells, and promote the infiltration of CD8 T cells to exert antitumour effects. Combination treatment with PD-L1 inhibitors can significantly prolong the survival time of mice. In conclusion, we found that nifuroxazide can inhibit the growth of glioblastoma and enhance antitumour immunity. [Display omitted] •Repurposing the antiprotozoal “old drug” nifuroxazide to the antineoplastic “new” drug” for glioma as a novel role of STAT3 inhibition.•Nifuroxazide-associated target gene and favorable GBM prognostic predictor-MAP3K1 and/or STAT3 induced cell cycle arrest, EMT, apoptosis in glioma with a favorable stability of toxicity profile.•Nifuroxazide can drive the M1 polarization of microglioma cells, inhibit the expression of CTLA4 and PD-L1 in tumour cells, and promote the infiltration of CD8 T cells to exert antitumour effects.•Nifuroxazide combined with PD-L1 inhibitor significantly prolonged the survival time of mouse glioma model. Glioblastoma is a primary intracranial tumour with extremely high disability and fatality rates among adults. Existing diagnosis and treatment methods have not significantly improved the overall poor prognosis of patients. Nifuroxazide, an oral antibiotic, has been reported to act as a tumour suppressor in a variety of tumours and to participate in the process of antitumour immunity. However, whether it can inhibit the growth of glioma is still unclear. Methods: We explored the potential mechanism of nifuroxazide inhibiting the growth of glioblastoma cells through in vitro and in vivo experiments. Results: nifuroxazide can inhibit the proliferation of glioblastoma cells, promote G2 phase arrest, induce apoptosis, and inhibit epithelial-mesenchymal transition through the MAP3K1/JAK2/STAT3 pathway. Similarly, clinical sample analysis confirmed that MAP3K1 combined with STAT3 can affect the prognostic characteristics of patients with glioma. In addition, nifuroxazide can drive the M1 polarization of microglioma cells, inhibit the expression of CTLA4 and PD-L1 in tumour cells, and promote the infiltration of CD8 T cells to exert antitumour effects. Combination treatment with PD-L1 inhibitors can significantly prolong the survival time of mice. Conclusion: we found that nifuroxazide can inhibit the growth of glioblastoma and enhance antitumour immunity. Thus, nifuroxazide is an effective drug for the treatment of glioblastoma and has great potential for clinical application.