Page 65 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P25

Overcoming paclitaxel-induced multidrug resistance in glioblastoma cells by using a
combination of metformin and bafilomycin A1

Sara Alves , Mariana Natalino , Jelena Dinić , Milica Pešić , M. Helena Vasconcelos 1,2,4
1,2
1,2
3
3
1 i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
2 Cancer Drug Resistance Group, IPATIMUP – Institute of Molecular Pathology and Immunology of the University of
Porto, Porto, Portugal
3 Department of Neurobiology, Institute for Biological Research “Siniša Stanković” - National Institute of Republic of
Serbia, University of Belgrade, Belgrade, Serbia
4 Department of Biological Sciences, FFUP – Faculty of Pharmacy, University of Porto, Porto, Portugal

Background: Glioblastoma (GBM) is the most frequent and aggressive malignant brain tumor, and is
associated with poor patient survival. Conventional GBM treatment includes surgery, radiotherapy and
chemotherapy, however drug resistance and relapse continue to occur which highlights the need for
alternative approaches. The use of autophagy modulators in combination with chemotherapeutic drugs
has potential therapeutic value. Material and methods: The effects of bafilomycin A1, an inhibitor of
lysosomal degradation, and metformin, a drug commonly used for type 2 diabetes treatment, that induces
autophagy through mTOR inhibition, were studied in GBM cell line U87 and its multidrug resistant
counterpart U87-TxR. The effects of bafilomycin A1 and metformin on autophagy, cell death, and cell
growth were evaluated by western blot, flow cytometry and SRB assay. Results: U87-TxR cells responded
differently to autophagy modulation, in comparison to sensitive parental U87 cells. Metformin induced cell
death in U87-TxR cells but not in U87, while bafilomycin A1 further enhanced metformin-induced cell death
of multidrug resistant cells. Furthermore, a co-treatment with metformin and bafilomycin A1 reversed
paclitaxel-induced resistance in multidrug resistant cells. Conclusion: These results suggest that metformin
and bafilomycin A1 could be used to enhance the cytotoxicity of classic chemotherapeutics and support
further research into compound combinations as a therapeutic approach that helps to overcome multidrug
resistance.
Keywords: bafilomycin A1; glioblastoma; metformin; multidrug resistance; paclitaxel

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