Rapamycin induces human acute promyelocytic leukemia cell HL-60 autophagic apoptosis

Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5506-5514. doi: 10.26355/eurrev_201712_13942.

Abstract

Objective: We aimed at investigating the effects of rapamycin on apoptosis and autophagy of human acute promyelocytic leukemia cell line HL-60, and to preliminarily explore the mechanism of extra medullary infiltration of leukemia cells with human acute promyelocytic leukemia cell line HL-60 as the object of study, providing a theoretical basis for the clinical treatment of leukemia.

Materials and methods: After HL-60 cells were cultured in vitro, the effect of rapamycin on proliferation ability of HL-60 cells was determined by methyl thiazolyl tetrazolium (MTT) method, the cell apoptosis ratio was detected by flow cytometer, the change of autophagy after HL-60 cells acted by rapamycin was tested by monodansylcadaverine (MDC) fluorescence staining, the mRNA expression of autophagy-related molecule was detected by polymerase chain reaction (PCR), and the expressions of apoptosis-related protein and autophagy-related protein were determined by Western blotting (WB).

Results: HL-60 cell proliferation could be significantly inhibited by rapamycin (80 μg/mL-640 μg/mL), which was in a dose-dependent manner. HL-60 cell apoptosis ratio and apoptosis-related protein expression were distinctly improved by rapamycin. Cell autophagy level, mRNA expression of autophagy-related molecule and autophagy-related protein expression were remarkably induced by rapamycin.

Conclusions: Rapamycin can induce HL-60 cell apoptosis, which is produced mainly by inducing cell autophagy.

MeSH terms

  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects
  • HL-60 Cells
  • Humans
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Sirolimus / pharmacology*

Substances

  • Autophagy-Related Protein 5
  • Microtubule-Associated Proteins
  • Caspase 3
  • Sirolimus