[Chemotherapeutic drugs enhanced rsTRAIL tumoricidal activity].
OBJECTIVE
To explore the role and mechanisms of chemotherapeutic drugs in TRAIL induced cell death.


METHODS
Tumoricidal activities of the chemotherapeutic drugs and/or rsTRAIL in 13 strains of tumor cell lines were evaluated by MTS-PMS assay and flow cytometry. DR5 expression in the cells was observed by Western blot.


RESULTS
The apoptosis of human promyelocytic leukemia cells HL-60, liver cancer cells BEL-7402, T-acute lymphoblastic leukemia cells Jurkat, and myeloid leukemia cells K562 treated with rsTRAIL at 0.5 microg/ml were 53.20%, 52.20%, 51.54%, 52.70%, and 41.00%, respectively, while that of the embryonal spleen cells 293 was 24.00%. However, the apoptosis percentages of lung cancer cells anti 973, breast cancer cells MCF-7, Chinese hamster ovarian cancer cells COS-7, neuroglialoma cells U251, neuroblastoma cells SH-SY5Y, glioma cells BT-325, rat pheochromocytoma cells PC12, and mouse adrenal epithelial cells NIH3T3 were all less than 10% under the same conditions. The sensitivity of central neuron cells of SH-SY5Y, PC-12, U251, BT3251, and human embryonal spleen cells 293, which were not sensitive to rsTRAIL challenges, increased remarkably after treatment with CHX, CP, and 8-CA at sub-toxic doses plus rsTRAIL at 0.5 microg/ml. The expressions of DR5 were up-regulated and kept pace with the onset of apoptosis in the BEL-7402 liver cancer cells.


CONCLUSIONS
The chemotherapeutic drugs including CHX, CP, and 8-CA at sub-toxic doses can enhance antitumor activity of rsTRAIL.
Wang
Ming-jie
MJ
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005, China.
Liu
Yan-xin
YX
Li
Xiao-ling
XL
Shi
Juan
J
Liu
Shi-lian
SL
Zheng
De-xian
DX
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D008175:Lung Neoplasms / Q000473:pathology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; C505655:Tnfsf10 protein, rat; D014409:Tumor Necrosis Factor-alpha