Dual Targeting of Anti-Apoptotic Proteins Enhances Chemosensitivity of the Acute Myeloid Leukemia Cells.
Apoptosis
Cell Line, Tumor
Etoposide
/ pharmacology
Humans
Inhibitor of Apoptosis Proteins
/ genetics
Leukemia, Myeloid, Acute
/ drug therapy
Myeloid Cell Leukemia Sequence 1 Protein
/ genetics
Proto-Oncogene Proteins c-bcl-2
/ genetics
RNA, Messenger
/ genetics
RNA, Small Interfering
/ genetics
Survivin
/ genetics
Etoposide
Mcl-1
Survivin
acute myeloid leukemia
siRNA
Journal
Asian Pacific journal of cancer prevention : APJCP
ISSN: 2476-762X
Titre abrégé: Asian Pac J Cancer Prev
Pays: Thailand
ID NLM: 101130625
Informations de publication
Date de publication:
01 Jul 2022
01 Jul 2022
Historique:
received:
11
04
2022
entrez:
28
7
2022
pubmed:
29
7
2022
medline:
2
8
2022
Statut:
epublish
Résumé
Acute myeloid leukemia (AML) is a type of blood cancer characterized by fast cellular proliferation. Myeloid cell leukemia-1 (Mcl-1) and survivin, as anti-apoptotic proteins, are involved in cancer growth and resistance to chemotherapy. The aim of this study was to examine the combination effect of Mcl-1 and survivin specific siRNAs on chemosensitivity of the human HL-60 AML cells. SiRNAs transfection was performed by using Lipofectamine™2000 reagent. The mRNA expression was analyzed by real-time quantitative PCR. The apoptosis analysis was measured by ELISA cell death assay. siRNAs markedly suppressed mRNA expression levels of Mcl-1 and survivin in a time-dependent manner, resulting in reduction of leukemic cell proliferation and enhanced spontaneous cell death. Surprisingly, Mcl-1 siRNA and survivin siRNA synergistically enhanced the cell toxic effects of etoposide. Furthermore, down-regulation of Mcl-1 and survivin significantly enhanced the apoptotic effect of etoposide. Our investigation suggests that suppression of Mcl-1 and survivin by siRNA can effectually inhibit cell growth and overcome chemoresistance of AML cells. Therefore siRNAs may be an important adjuvant in chemotherapy for AML patients.
Sections du résumé
BACKGROUND
BACKGROUND
Acute myeloid leukemia (AML) is a type of blood cancer characterized by fast cellular proliferation. Myeloid cell leukemia-1 (Mcl-1) and survivin, as anti-apoptotic proteins, are involved in cancer growth and resistance to chemotherapy. The aim of this study was to examine the combination effect of Mcl-1 and survivin specific siRNAs on chemosensitivity of the human HL-60 AML cells.
METHODS
METHODS
SiRNAs transfection was performed by using Lipofectamine™2000 reagent. The mRNA expression was analyzed by real-time quantitative PCR. The apoptosis analysis was measured by ELISA cell death assay.
RESULTS
RESULTS
siRNAs markedly suppressed mRNA expression levels of Mcl-1 and survivin in a time-dependent manner, resulting in reduction of leukemic cell proliferation and enhanced spontaneous cell death. Surprisingly, Mcl-1 siRNA and survivin siRNA synergistically enhanced the cell toxic effects of etoposide. Furthermore, down-regulation of Mcl-1 and survivin significantly enhanced the apoptotic effect of etoposide.
CONCLUSIONS
CONCLUSIONS
Our investigation suggests that suppression of Mcl-1 and survivin by siRNA can effectually inhibit cell growth and overcome chemoresistance of AML cells. Therefore siRNAs may be an important adjuvant in chemotherapy for AML patients.
Identifiants
pubmed: 35901361
doi: 10.31557/APJCP.2022.23.7.2523
pmc: PMC9727342
pii:
doi:
Substances chimiques
Inhibitor of Apoptosis Proteins
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Proto-Oncogene Proteins c-bcl-2
0
RNA, Messenger
0
RNA, Small Interfering
0
Survivin
0
Etoposide
6PLQ3CP4P3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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