Down-regulation of NOTCH1 and PKM2 can inhibit the growth and metastasis of colorectal cancer cells.

Jia Wang, Meijuan Sun, Rong Ma, Gaobo Wang, Wenqing Li, Bowei Yang, Yang Yang

Journal:American Journal of Translational Research

IF:3.94

DOI:PMID:36105047

PMID:36105047

Published:2022-08-15

research field:肿瘤学

Abstract

Background Previous studies have revealed the overexpression of Notch receptor 1 (NOTCH1) and pyruvate kinase M2 (PKM2) in colorectal cancer (CRC) tissue and their relationship to disease development. However, whether there is synergy between PKM2 and NOTCH1 needs to be verified. This study aims to analyze the mechanism and relationship between NOTCH1 and PKM2 in CRC. Methods Immunohistochemistry was used to measure the expression of NOTCH1 and PKM2 in colorectal cancer, and the correlation between them was analyzed by Pearson test. The protein and mRNA expressions in CRC cell lines were determined by western blot (WB) and real-time quantitative reverse transcription PCR (qRT-PCR). Compound 3K and tangeretin (TGN) were used to inhibit the expressions of PKM2 and NOTCH1, respectively. The wound healing assay and CCK-8 assay were applied to measure the migration and proliferation of cancer cells. Results Immunohistochemical analysis showed that NOTCH1 and PKM2 were overexpressed in patients with colorectal cancer, and patients with overexpression showed a higher number of lymph node metastases and high tumor stage (III+IV) (P<0.05). In addition, Pearson test showed that the level of NOTCH1 was positively correlated with the level of PKM2 (P<0.05). WB and qRT-PCR showed that the protein and mRNA levels of NOTCH1 and PKM2 in colorectal cancer cells were significantly up-regulated (P<0.05). The inhibition of PKM2 and NOTCH1 had a synergistic effect on reducing the invasion and proliferation of CRC cells. Conclusion NOTCH1 and PKM2 are highly expressed in CRC patients. Inhibiting the expression of NOTCH1 and PKM2 can inhibit the growth and metastasis of CRC cells, providing therapeutic targets for the treatment of CRC.

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