PRIMA-1(MET) Induces Cellular Senescence and Apoptotic Cell Death in Cholangiocarcinoma Cells

PRIMA-1(MET)诱导胆管癌细胞衰老和凋亡

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Abstract

BACKGROUND/AIM: This study examined the in vitro effects of the bile duct cancer drug PRIMA-1(MET) on cholangiocarcinoma (CCA) cell growth to determine its potential usefulness in CCA therapy. MATERIALS AND METHODS: The effect of this drug on the expression of senescent markers (p16(INK4A) and p21) and the phosphorylation of p53 was investigated, as was the association between senescent markers and the patients' clinicopathological data. RESULTS: PRIMA-1(MET) inhibited CCA cell growth with the half maximal-inhibitory concentration (IC(50)) values of 21.9-40.8 μM. PRIMA-1(MET) induced phospho-p53, p16(INK4A) and p21 triggering cellular senescence and apoptosis. High expressions of p16(INK4A) and p21 were associated with a high survival rate of patients with CCA. CONCLUSION: PRIMA-1(MET) may potentially be an alternative anticancer agent that might lead to a better prognosis in patients with CCA.

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