Background <p>Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor response to chemotherapy such as Carboplatin, mainly due to drug resistance and systemic toxicity. Recent studies suggest that probiotics like Bifidobacterium reuteri may have anti-tumor properties and enhance the efficacy of chemotherapy. This study evaluates the potential of <i>B. reuteri</i> Ab.338 SH (GenBank: PV961363), isolated from traditional yogurt, in potentiating Carboplatin’s effects on U-87 MG glioblastoma cells.</p> Methods <p><i>B. reuteri</i> Ab.338 SH was isolated and molecularly characterized. U-87 MG cells were treated with Carboplatin, <i>B. reuteri</i>, and their combination. Cell viability was evaluated by MTT assay, apoptosis by Annexin V-FITC/PI staining and flow cytometry, and gene expression of apoptosis-related markers by qRT-PCR. Selectivity was confirmed using HUVEC cells as a normal control.</p> Results <p>T treatment markedly reduced the effective dose of Carboplatin and enhanced apoptosis compared with either treatment alone. Flow cytometry showed increased late apoptotic cells with co-treatment. qRT-PCR analysis revealed upregulation of pro-apoptotic genes (he combination<i>BAX</i>,<i> Caspase-3/8/9</i>,<i> Fas</i>,<i> PTEN</i>,<i> IκB</i>,<i> P53</i>,<i> P21</i>) and downregulation of <i>AKT</i>,<i> mTOR</i>, and <i>Bcl-2. B. reuteri</i> alone showed no cytotoxicity toward normal endothelial cells.</p> Conclusion <p><i>B. reuteri</i> Ab.338 SH enhances Carboplatin efficacy in GBM cells while lowering its required dose and potential toxicity. This probiotic may serve as a promising adjuvant in GBM therapy, warranting further in vivo validation.</p> Graphical abstract <p></p>

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Bifidobacterium enhances the antitumor efficacy of carboplatin in glioblastoma cells: targeting apoptotic and cell cycle regulatory pathways via Caspase, AKT/PTEN, and P53/P21 signaling

  • Abbas Asoudeh-Fard,
  • Moein Yeylagh-Beygi,
  • Mohadeseh Asoudeh-Fard,
  • Mohammad Abbasi,
  • Mohammad Bagher Nazari,
  • Ahmad Gholami,
  • Asghar Parsaei

摘要

Background

Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor response to chemotherapy such as Carboplatin, mainly due to drug resistance and systemic toxicity. Recent studies suggest that probiotics like Bifidobacterium reuteri may have anti-tumor properties and enhance the efficacy of chemotherapy. This study evaluates the potential of B. reuteri Ab.338 SH (GenBank: PV961363), isolated from traditional yogurt, in potentiating Carboplatin’s effects on U-87 MG glioblastoma cells.

Methods

B. reuteri Ab.338 SH was isolated and molecularly characterized. U-87 MG cells were treated with Carboplatin, B. reuteri, and their combination. Cell viability was evaluated by MTT assay, apoptosis by Annexin V-FITC/PI staining and flow cytometry, and gene expression of apoptosis-related markers by qRT-PCR. Selectivity was confirmed using HUVEC cells as a normal control.

Results

T treatment markedly reduced the effective dose of Carboplatin and enhanced apoptosis compared with either treatment alone. Flow cytometry showed increased late apoptotic cells with co-treatment. qRT-PCR analysis revealed upregulation of pro-apoptotic genes (he combinationBAX, Caspase-3/8/9, Fas, PTEN, IκB, P53, P21) and downregulation of AKT, mTOR, and Bcl-2. B. reuteri alone showed no cytotoxicity toward normal endothelial cells.

Conclusion

B. reuteri Ab.338 SH enhances Carboplatin efficacy in GBM cells while lowering its required dose and potential toxicity. This probiotic may serve as a promising adjuvant in GBM therapy, warranting further in vivo validation.

Graphical abstract