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Targeted apoptosis induction of antiMRP3(scFv)-sTRAIL toward glioblastoma multiforme
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Abstract:
Objective: To observe the effects of antiMRP3(scFv)-sTRAIL on apoptosis in glioblastoma multiforme (GBM) U251 cells and to study its mechanism. Methods: Different concentration of antiMRP3(scFv)-sTRAIL (3.9063 nmol/L-250 nmol/L) was added into U251 cells, and then the viability was examined by MTT assay. IC50 dose of antiMRP3(scFv)-sTRAIL was added into U251 cells, in the presence or absence of parental antiMRP3(scFv) and the TRAIL-neutralizing mAb 2E5. The apoptotic percentage of U251 cells was examined by flow cytometry, and Western blotting was used to detect caspase-3 activation and DNA fragmentation factor (DFF) degradation in U251 cells. Results: When the concentration of antiMRP3(scFv)-sTRAIL increased (3.9063 nmol/L-250 nmol/L), the viability of U251 cells became lower synchronously (\[84.84±0.2\]%-\[19.93±1.8\]%); The apoptotic rates of U251 cells induced by IC50 dose (62.5 nmol/L) of antiMRP3(scFv)-sTRAIL or antiMRP3(scFv)-sTRAIL with parental antiMRP3(scFv) and mAb 2E5 were (58.0±1.3)%, (14.9±1.7)% and (17.4±3.0)%, respectively; antiMRP3(scFv) and the mAb 2E5 significantly inhibited the activation of caspase-3 and the degradation of DFF in U251 cells induced by antiMRP3(scFv)-sTRAIL. Conclusion: Targeted binding of antiMRP3(scFv)-sTRAIL to GBM increases the apoptosis induction activity of sTRAIL, which lays a foundation for further study on tumor-targeting drugs.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 30571906), and the Major Science and Technology Special Project for “Significant New Drug Creation” of China (No. 2009ZX09102-234；No. 2009ZX09103-689)
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