Background Studies have shown that pyruvate kinase M2 (PKM2) and Notch1 are highly expressed in colorectal cancer (CRC) tissues and have a certain relationship with disease occurrence and development. The expression levels of PKM2 and Notch1 are also related to the effect of chemotherapy and radiotherapy, which seriously influence the prognosis of CRC patients. Thus, both PKM2 and Notch1 have been identified as key targets of CRC treatment and research. However, correlations between PKM2 and Notch1 have not yet been established.
Methods Immunohistochemical analysis was conducted to detect the expression of PKM2 and Notch1 in CRC tissues. The mRNA and protein expression levels of PKM2 and Notch1 in CRC cell lines were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. Compound 3K and tangeretin (TGN) were used to inhibit the expression of PKM2 and Notch1, respectively. The proliferation and migration of cancer cells in each group were detected with the CCK-8 and wound healing assays.
Results The Immunohistochemical analysis showed that PKM2 and Notch1 were highly expressed in CRC and related to tumor stage and lymph node metastasis. The qRTPCR and western blot results showed that PKM2 and Notch1 were notably upregulated in CRC cells both at the mRNA and protein levels. PKM2 and Notch1 form a positive feedback loop to promote the occurrence and development of CRC, and inhibition of PKM2 and Notch1 has a synergistic effect on the proliferative and invasive capabilities of CRC cells.
Conclusion The combination of the PKM2 inhibitor compound 3K and the Notch1 inhibitor TGN presents a novel and effective strategy for treatment of CRC.