Study On The Mechanism Of Metformin Combined Anti-EN01 Antibody Reverse Cisplatin Or Cetuximab Therapeutic Resistance

Numerous studies have shown that cancer stem cells have led to acquired resistance to traditional chemotherapy or targeted therapy,greatly affecting the effectiveness of chemotherapy and targeted therapy,and how resistance to reverse chemotherapy or targeted therapy by targeting cancer stem cells is of great significance to the long-term treatment of tumors.Based on a large number of literature research and pre-laboratory research,this study used metformin,anti-ENO1 antibodies combined cisplatin to treat gastric cancer PAMC82 cells,combined with cetuximab treat non-small cell lung cancer A549 cells,through cell flow cytometry and cell function experiments.It was found that metformin was able to target the ALDH+cancer stem cell,and the anti-ENO1 antibody was able to target the CD44+ cancer stem cell,both of which alone could not effectively reverse the acquired resistance of cisplatin or cetuximab.Metformin combined anti-ENO1 antibodies can target both ALDH+and CD44+cancer stem cell,inhibit the proliferation potential,migration capacity,invasive capacity and self-renewal ability of cancer cells,and demonstrate strong synergistic inhibition of tumor cells when used in combination with cisplatin or cetuximab.We further explore the mechanisms of metformin,anti-ENO1 antibodies targeting ALDH+and CD44+ cancer stem cell subpopulation and synergistic inhibitions through western blot and immunofluorescence.It was found that metformin can target the ALDH+cancer stem cell subpopulation by activating the AMPK signaling pathway,and the anti-ENO1 antibody can target the CD44+cancer stem cell subgroup by inhibiting the PI3K/AKT signal pathway,and the WNT signal pathway is inhibited when metformin,anti-ENO1 antibody combined cisplatin or cetuximab,p-GSK3β expression is upregulated,p-β-catenin expression was downregulated,through immunofluorescence we found that the p-catenin expression in the nucleus downregulated,suggesting that the three drugs can be combined treatment through GSK3 β/β-catenin inhibition β-catenin to play the role of transcription co-activator,resulting in synergistic inhibition.