[The expression of Fas, FasL and Bcl-2 on RMA cells during the process of apoptosis induced by chemotherapeutic drugs].
The objective of the study is to explore the effect of Fas, FasL and Bcl-2 on the process of apoptosis induced by chemotherapeutic drugs through detecting the expression of Fas, FasL and Bcl-2 on murine lymphoma cell line RMA. Dexamethasone(DEX), etoposide (VP-16), arsenic trioxide As(2)O(3) and all trans-retinoic-acid (ATRA) were added to the RMA cells as well as to the cells preincubated with interleukin-2 (IL-2), interleukin-6 (IL-6) or granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. The effect on apoptosis was observed and the expression of Fas and FasL mRNA as well as the expression of Fas and Bcl-2 antigen were measured. DEX and VP-16 could promote apoptosis of RMA cells while upregulating the expression of Fas and FasL without affecting the expression of Bcl-2. ATRA downregulated the expression of Bcl-2 without any change of Fas and FasL, and no apoptosis of RMA cells induced by ATRA was observed. Although As(2)O(3) induced apoptosis of RMA cells, it did not affect the expression of Fas, FasL and Bcl-2, which suggested that different drugs induce apoptosis of the same kind of cells by different signal transduction system and apoptosis induced by Fas system needed the coexistence of Fas and FasL. Although IL-2, IL-6 and GM-CSF upregulated the expression of Fas protein when adding to RMA cells separately, none of them induced apoptosis. Apoptosis could be induced by combination of IL-2 and IL-6 along with the upregulation of Fas and FasL. The cytokines facilitated the apoptotic action of chemotherapeutic drugs, the drug concentration for inducing apoptosis decreased and the time period of starting apoptosis shortened. Apoptosis could be observed without the expression of FasL when anti-Fas-antibody was added to RMA cells. The results demonstrated that there was synergistic effect of chemotherapeutic drugs and some cytokines for induction of apoptosis. Fas-FasL system participated in the apoptosis induced by DEX and VP-16; different drugs induce apoptosis by different pathway of signal transduction.
Zhu
Hong-Li
HL
Department of Nanlou Hematology, The General Hospital of PLA, Beijing 100853, China.
Wang
Yue-Zeng
YZ
Yu
Li
L
Li
Bin
B
Yao
Shan-Qian
SQ
Lou
Fang-Ding
FD
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D053222:Fas Ligand Protein; D015870:Gene Expression / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D010087:Oxides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis*
D001152:Arsenicals; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D014212:Tretinoin; D005047:Etoposide; D003907:Dexamethasone; D000077237:Arsenic Trioxide