Jia Wang1, Meijuan Sun2, Rong Ma3, Gaobo Wang1, Wenqing Li1, Bowei Yang1, Yang Yang1. 1. Department of General Surgery, Baoji City People's Hospital Baoji 721000, Shaanxi, China. 2. Department of Pharmacy, Baoji Second People's Hospital Baoji 721000, Shaanxi, China. 3. Department of Pathology, Baoji City People's Hospital Baoji 721000, Shaanxi, China.
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. AJTR
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. AJTR
Authors: Carina Ulvklo; Ryan MacDonald; Caroline Bivik; Magnus Baumgardt; Daniel Karlsson; Stefan Thor Journal: Development Date: 2012-01-12 Impact factor: 6.868
Authors: John J Arcaroli; W M Tai; Ryan McWilliams; Stacey Bagby; Patrick J Blatchford; Marileila Varella-Garcia; Alicia Purkey; Kevin S Quackenbush; Eun-Kee Song; Todd M Pitts; Dexiang Gao; Chris Lieu; Martine McManus; Aik Choon Tan; Xianxian Zheng; Qin Zhang; Mark Ozeck; Peter Olson; Zhi-Qin Jiang; Scott Kopetz; Antonio Jimeno; Stephen Keysar; Gail Eckhardt; Wells A Messersmith Journal: Int J Cancer Date: 2015-07-22 Impact factor: 7.396