Synergistic antitumor activity of TRAIL combined with mevastatin in glioma SWO-38 cell line and its mechanism

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Author:
ZHONG Fei(Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China)
WU Xiang-yuan(Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China)
YANG Jing()
LIN Qu(Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China)
DONG Ming(Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China)
WEN Jing-yun(Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China)
Journal Title:
CHINESE JOURNAL OF NEUROMEDICINE
Issue:
Volume 8, Issue 12, 2009
DOI:
10.3760/cma.j.issn.1671-8925.2009.12.005
Key Word:
Tumor necrosis factor-related apoptosis-inducing ligand; Mevastatin; Glioma; Proliferation; Apoptosis

Abstract: Objective To investigate the effects of tumor necrosis-related apoptosis-inducing ligand (TRAIL), mevastatin, or their combinations on the proliferation and apoptosis in glioma SWO-38 cells and their mechanisms. Methods The human glioma cell line SWO-38 was treated with human recombinant soluble TRAIL (rsTRAIL) and mevastatin, respectively, or their combinations. The proliferation of SWO-38 cells was analyzed with MTT assay; the cell apoptosis was detected by flow cytometry (Annexin V-FTTC-PI assay); the expressions of TRAIL R1/DR4 and TRAIL R2/DR5 on the cell surface were determined by indirect fluorescence staining and flow cytometry analysis; the mRNA expressions of TRAIL R1/DR4 and TRAIL R2/DR5 were detected by reverse transcription-polymerase chain reaction. Results The rsTRAIL and mevastatin, used alone or in combination, inhibited the cell proliferation of SWO-38 cells and induced their apoptosis in a time- and dose-dependent manner. The combination of rsTRAIL and mevastatin remarkably inhibited the proliferation and induced the apoptosis as compared with the rsTRAIL or mevastatin alone (P<0.05). Seventy-two hours after treatment, the expressions of TRAIL R1/DR4 and TRAIL R2/DR5 in the treatment groups were significantly higher as compared to those in the normal control group, and so was their mRNA expression level (P<0.05). Conclusion Both rsTRAIL and mevastatin can inhibit the proliferation and induce the apoptosis of SWO-38 cell; their combinations have a synergistic effect probably through the up-regulation of TRAIL R1/DR4 and TRAIL R2/DR5 expressions and their mRNA expressions on cell surface.

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