Inhibition of SCD1 Activity Blocks Cell Cycle Progression and Impairs Proliferation in Breast Cancer Cells

Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition)..

OBJECTIVE: To investigate the expression of stearoyl-CoA desaturase-1 (SCD1) in breast cancer cell lines. To analyze the effect of inhibiting SCD1 activity on the proliferation and cell cycle of MCF-7 breast cancer cell and its mechanism.

METHODS: The expression of SCD1 protein were detected by Western blot techniques in breast cancer cell lines and humanskin fibroblasts.Cell viability of MCF-7 cells treated with MF-438 was measured using MTS assay and IC50 value was calculated.The distribution of cell cycle was determined by PI staining using flow cytometry.The expression of Cyclin D1 was detected by Western blot. The expression of Akt, pAkt, pAMPK and pACC were also detected by Western blot.

RESULTS: The expression level of SCD1 in MCF-7 and MDA-MB-231 cells was significantly higher than that in HSF cells (P < 0.05).MF-438 showed a significant dose-dependent proliferation inhibition effect on MCF-7 cells cultured in low serum at a concentration ranging from 100 nmol/L to 100 μmol/L with an IC50 value of (3.9±0.45) μmol/L. After intervention of 5 μmol/L MF-438 in MCF-7 cells, the proportion of cells in S phase and G2/M phase was significantly decreased (P < 0.01), the proportion of cells in G0/G1 phase increased (P < 0.01), and the expression of Cyclin D1 was significantly decreased (P < 0.05); Meanwhile, the expression of pAkt and pAkt/Akt value were significantly decreased (P < 0.05) and the expression of pAMPK and pACC levels were significantly increased (P < 0.05).

CONCLUSIONS: SCD1 plays an important role in the occurrence and development of breast cancer. Inhibition of SCD1 activity can inhibit cell cycle progression and impair cell proliferation by down-regulating the Akt pathway and activating the AMPK pathway. Further research on SCD1 is expected to provide a new target for molecular targeted therapy of breast cancer.

Medienart:

Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:50

Enthalten in:

Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition - 50(2019), 4 vom: 21. Juli, Seite 546-550

Sprache:

Chinesisch

Beteiligte Personen:

Zhao, Jing [VerfasserIn]
Zhang, Li-Tao [VerfasserIn]
Bai, Yun [VerfasserIn]
Wang, Ze-Yang [VerfasserIn]
Zhang, Xue-Mei [VerfasserIn]
Ma, Chun-Ling [VerfasserIn]

Themen:

136601-57-5
AMP-Activated Protein Kinase Kinases
Breast cancer
CCND1 protein, human
Cell cycle
Cyclin D1
EC 1.14.19.1
EC 2.7.-
EC 2.7.11.1
EC 2.7.11.3
Fatty acid
Journal Article
Proliferation
Protein Kinases
Proto-Oncogene Proteins c-akt
SCD1
SCD1 protein, human
Stearoyl-CoA Desaturase

Anmerkungen:

Date Completed 14.11.2019

Date Revised 04.12.2021

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM302483365