[Effects of all-trans retinoic acid and arsenic trioxide on tissue factor expression of acute promyelocytic leukemia cells].

Abstract

OBJECTIVE:

To investigate the effects of all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on both tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro.

METHODS:

The PCA of APL blasts freshly isolated from the APL patients treated with ATRA or As(2)O(3) was detected using a one-stage clotting assay; the TF antigen was detected by ELISA and TF mRNA by RT-PCR. The maturation sensitivity (NB4) or resistant subclones (NB4-R1) of the promyelocytic NB4 cell line as well as U937 cells transfected with pMSCV-PML-RARa treated with or without ATRA or As(2)O(3) were also examined.

RESULTS:

Both ATRA and As(2)O(3) time-dependently down-regulated the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro. The TF antigen level in PML-RARa(+) U937 cells was significantly higher than that in U937 cells transfected with retrovirus vector (890 pg/8 x 10(5) +/- 80 pg/8 x 10(5) cell and 728 pg/8 x 10(5) +/- 86 pg/8 x 10(5) cell, respectively). Both ATRA and As(2)O(3) down-regulated the TF antigen of the U937 cells transfected with or without PML-RARa.

CONCLUSION:

Tissue factor expression and PCA of APL cells can be down-regulated by ATRA and As(2)O(3). By down-regulating the TF expression, As(2)O(3) might also be used to improve the DIC-related hemorrhage of APL. It is also suggested that elevated TF antigen in the PML-RARa(+) U937 cells may be related with the fusion protein PML-RARa, while the down-regulation effect of ATRA and As(2)O(3) on the TF expression of U937 cells might not be involved in the fusion protein.

• Authors: W Guo, H Wang, W Zhao
• Journal: Zhonghua yi xue za zhi (Zhonghua Yi Xue Za Zhi) Vol. 80 Issue 5 Pg. 327-31 (May 2000) ISSN: 0376-2491 [Print] China
• PMID: 11798779 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Arsenicals
• Neoplasm Proteins
• Oncogene Proteins, Fusion
• Oxides
• RNA, Messenger
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
• Tretinoin
• Thromboplastin
• Arsenic Trioxide

Topics

• Adolescent
• Adult
• Antineoplastic Agents (pharmacology, therapeutic use)
• Arsenic Trioxide
• Arsenicals (pharmacology, therapeutic use)
• Blood Coagulation (drug effects)
• Cells, Cultured
• Female
• Gene Expression (drug effects)
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, genetics)
• Leukocytes, Mononuclear (cytology, drug effects)
• Male
• Middle Aged
• Neoplasm Proteins (genetics)
• Oncogene Proteins, Fusion (genetics)
• Oxides (pharmacology, therapeutic use)
• RNA, Messenger
• Thromboplastin (biosynthesis, genetics)
• Transcription, Genetic (drug effects)
• Tretinoin (pharmacology, therapeutic use)
• Tumor Cells, Cultured
• U937 Cells