Chemotherapeutic drugs enhanced rsTRAIL tumoricidal activity / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>To explore the role and mechanisms of chemotherapeutic drugs in TRAIL induced cell death.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>The chemotherapeutic drugs including CHX, CP, and 8-CA at sub-toxic doses can enhance antitumor activity of rsTRAIL.</p>