MCM7 affects the cisplatin resistance of liver cancer cells and the development of liver cancer by regulating the PI3K/Akt signaling pathway.

Autor: Su D; Department of Infectious Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
Jazyk: angličtina
Zdroj: Immunopharmacology and immunotoxicology [Immunopharmacol Immunotoxicol] 2022 Feb; Vol. 44 (1), pp. 17-27. Date of Electronic Publication: 2021 Nov 25.
DOI: 10.1080/08923973.2021.1991372
Abstrakt: Objective: Aberrant DNA replication is regarded as a component of cancer development. Minichromosome maintenance protein 7 (MCM7), which is critical for the initiation of DNA replication, is overexpressed in multiple malignancies. The effect of MCM7 on cell proliferation, apoptosis, and drug resistance of liver cancer and its mechanism were investigated in this study.
Methods: MCM7 expression in normal liver cells, liver cancer cell lines, and tissues, as well as adjacent tissues, was determined by qRT-PCR. CCK-8 and flow cytometry was performed to detect cell viability, apoptosis, and cell cycle, respectively. The related mRNA and protein expressions were detected by qRT-PCR and western blot.
Results: High expression of MCM7 was found in liver cancer tissues and cells, which results in notably lower survival time of patients. Cisplatin (DDP) could inhibit cell proliferation and affect MCM7 expression. Silencing of MCM7 inhibited cell viability, promoted cell apoptosis, arrested cell cycle at G1 phase, and enhanced the effect of DDP on cancer cells, while overexpression of MCM7 did the opposite. Moreover, silencing of MCM7 inhibited cyclinD1 and Ki-67 expressions. The overexpression of MCM7 increased phosphorylation levels of PI3K and AKT, activated the PI3K/AKT pathway, and weakened the inhibitory effect of DDP on the PI3K/AKT pathway.
Conclusion: Silencing of MCM7 may inhibit cell proliferation and promote apoptosis by regulating the PI3K/AKT pathway to affect the cell cycle, thus affecting the development of liver cancer, and improving the sensitivity of liver cancer cells to DDP.
Databáze: MEDLINE
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