Effect of obatoclax in combination with 5-fluorouracil on the apoptosis of pancreatic cancer cells under hypoxic

Abstract

Abstract:

AIM: To explore the effects of OBX combined with 5-FU on pancreatic cancer cell apoptosis (HPAC), and its possible mechanism. METHODS: Hypoxic condition was established. Western blot method was used to detect the expression of HIF-1α in HPAC cells under normal oxygen and hypoxia condition. Hoechest33258 staining was applied to analyze the effects of OBX on apoptosis of HPAC cells under normal oxygen and hypoxia condition. MTT assay was used to detect cell viability in hypoxic group, 5-FU group and OBX combined with 5-FU group. Western blot was applied to detect HIF-1α, Bcl-2 and Bax proteins expression in HPAC cells of hypoxic group, 5-FU group and OBX combined with 5-FU group. RESULTS:Under hypoxia condition, the expression of HIF-1α in HPAC cells was much higher than its expression under normal oxygen. The effect of OBX on HPAC cells apoptosis enhanced with dose-dependent in a certain range of concentrations. Under hypoxia condition, 5-FU decreased pancreatic cancer cells viability and reduced the expressions of HIF-1α, Bcl-2 proteins, but promoted the expression of Bax protein in HPAC cells. OBX combined with 5-FU enhanced the inhibitive effects on cells viability. The expressions of HIF-1α, Bcl-2 proteins reduced further, but the expression of Bax protein increased significantly. CONCLUSION: Under hypoxia condition, OBX combined with 5-FU can enhance the inhibition on HPAC cells viability, and the induction on HPAC cells apoptosis, the mechanism maybe related to reduce the expressions of HIF-1α, Bcl-2 proteins and increasing Bax expression.

Key words: pancreatic cancer, hypoxia, obatoclax, 5-fluorouracil, apoptosis

CLC Number:

R965.2

SONG Haiyan, ZHANG Yimin, ZHOU Zhixin, CHENG Huixin, FU Shengqi. Effect of obatoclax in combination with 5-fluorouracil on the apoptosis of pancreatic cancer cells under hypoxic[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(8): 887-891.

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