Notch signaling via regulation of RB and p-AKT but not PIK3CG contributes to MIA PaCa-2 cell growth and migration to affect pancreatic carcinogenesis

作者：Zhang, Shubing; Liu, Jingjiang; Xu, Keli; Li, Zhijian^*

来源：Oncology Letters, 2018, 15(2): 2105-2110.

DOI：10.3892/ol.2017.7551

• Notch signaling
• retinoblastoma protein
• phosphoinositide-3 kinase catalytic subunit-gamma
• SMAD family member 2
• pancreatic cancer

Pancreatic cancer is one of the leading causes of cancer-associated mortality. The understanding of the expression pattern of key protein factors and their function in pancreatic cancer cells is therefore vital for the diagnosis and treatment of this malignancy. The results of the present study reveal that the levels of neurogenic locus notch homolog protein 2 (Notch2) and phosphorylated (p)-SMAD family member 2 decreased, whereas the expression of Notch3 and phosphoinositide-3 kinase catalytic subunit-gamma protein increased in human pancreatic cancer tissues compared with tumor-adjacent tissues. Using the human pancreatic cancer MIA PaCa-2 cell line, it was observed that retinoblastoma-associated protein (RB) and p-RB expression were inhibited and p-AKT was upregulated when Notch signaling was activated in MIA PaCa-2 cells. Furthermore, inhibition of phosphoinositide-3 kinase catalytic subunit-y (PIK3CG) activity by AS-605240 was able to block the growth and migration of MIA PaCa-2 cells. In conclusion, the results of the present study demonstrate that the Notch signal pathway may be involved in pancreatic carcinogenesis by modulating RB and p-AKT. PIK3CG may therefore be a potential target gene for the treatment of pancreatic cancer.

• 出版日期2018-2
• 单位中南大学