Zhu, Xiaodong
(Department of Chemotherapy, Tumor Hospital, Department of Oncology, Shanghai Medical College, Fudan University)
,
Lin, Gengjin
(Department of Gastroenterology, Hushan Hospital, Fudan University)
,
Zhu, Tengfang
(Department of Pathology, Shanghai Medical College, Fudan University)
,
Li, Jin
(Department of Chemotherapy, Tumor Hospital, Department of Oncology, Shanghai Medical College, Fudan University)
,
Cheng, Lvchou
(Department of Chemotherapy, Tumor Hospital, Department of Oncology, Shanghai Medical College, Fudan University)
,
Chen, Liying
(Department of Chemotherapy, Tumor Hospital, Department of Oncology, Shanghai Medical College, Fudan University)
Purpose To identify the antitumor effect of survivin antisense oligodeoxynucleotides (AS-ODN) in vitro and in vivo,and whether synergism exists between survivin AS-ODN and taxol. Methods Sense and antisense survivin oligodeoxynucleotides were transfected into BGC-823 cells by lipofect amine me-diate...
Purpose To identify the antitumor effect of survivin antisense oligodeoxynucleotides (AS-ODN) in vitro and in vivo,and whether synergism exists between survivin AS-ODN and taxol. Methods Sense and antisense survivin oligodeoxynucleotides were transfected into BGC-823 cells by lipofect amine me-diated transient transfection method. Taxol was administrated to both transfected and untransfected cells. Cell proliferation was measured by MTT method and survivin expression was detected by Western Blot. In animal experiment, 65 six-week-old Wistar rats were fed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) so-lutions and a diet supplemented with 8% NaCl in order to induce gastric cancer. At the end of week 20, these rats were divided into 4 groups randomly: the control group (C) ,20 rats.no therapy were used; the taxol group(T) ,15 rats were given ip injections of taxol at a dose of 10 mg/kg every other week; the anti-sense group(A) ,15 rats were given ip injections of an survivin AS-ODN lipofect amine complex at a dose of 50 fig/kg every 72 hours;taxol associated with antisense group(AT) ,15 rats were given i. p. injections of taxol and survivin AS-ODN as group T and A. At the end of week 35 ,all the surviving rats were killed. The incidence of gastric cancer in each group were calculated. The Brdu labeling index and apoptosis index in gas-tric cancer tissues of each group were detected with immunohistochemical analysis and TUNEL,respectively. Results About 50% reduction of survivin expression and inhibition of cell prolife-ration with an IC51) at 350 nmol/L were noted in the survivin AS-ODN transfected cells while little effects noted in the sense ODN transfected cells. The combination of transfection survivin AS-ODN with taxol significantly reduced the IC50 of taxol from 60 ng/mL to 2.4 ng/mL.The incidence of gastric cancer in C,T,A,and AT group is 90% , 78.6% ,73.3% ,and 50% respectively. The incidence of AT group was significantly lower than that of C group (P < 0. 05). The BrdU labeling index of AT was 10.2 ± 4.7 , and was significantly lower than that of C group( 18.7 ± 5.5, P<0.05) and T,A group (16.0 ± 5. 8 ,15.4 ± 5.2,P<0.05). The apoptosis index of gastric cancer tissues in AT group were 1.71 ±0.41, and were significantly lower than that of C group (0.91 ±0.14) and T,A group (1.19 ± 0.42,1.29 + 0.43,P<0. 05). Conclusions Both in vitro and in viva, combination of taxol with transfection survivin AS-ODN can get synergetic antitumor effect by re-ducing cell proliferation and augmenting apoptosis.This suggests that survivin is an effective target of antitu-mor therapy.
Purpose To identify the antitumor effect of survivin antisense oligodeoxynucleotides (AS-ODN) in vitro and in vivo,and whether synergism exists between survivin AS-ODN and taxol. Methods Sense and antisense survivin oligodeoxynucleotides were transfected into BGC-823 cells by lipofect amine me-diated transient transfection method. Taxol was administrated to both transfected and untransfected cells. Cell proliferation was measured by MTT method and survivin expression was detected by Western Blot. In animal experiment, 65 six-week-old Wistar rats were fed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) so-lutions and a diet supplemented with 8% NaCl in order to induce gastric cancer. At the end of week 20, these rats were divided into 4 groups randomly: the control group (C) ,20 rats.no therapy were used; the taxol group(T) ,15 rats were given ip injections of taxol at a dose of 10 mg/kg every other week; the anti-sense group(A) ,15 rats were given ip injections of an survivin AS-ODN lipofect amine complex at a dose of 50 fig/kg every 72 hours;taxol associated with antisense group(AT) ,15 rats were given i. p. injections of taxol and survivin AS-ODN as group T and A. At the end of week 35 ,all the surviving rats were killed. The incidence of gastric cancer in each group were calculated. The Brdu labeling index and apoptosis index in gas-tric cancer tissues of each group were detected with immunohistochemical analysis and TUNEL,respectively. Results About 50% reduction of survivin expression and inhibition of cell prolife-ration with an IC51) at 350 nmol/L were noted in the survivin AS-ODN transfected cells while little effects noted in the sense ODN transfected cells. The combination of transfection survivin AS-ODN with taxol significantly reduced the IC50 of taxol from 60 ng/mL to 2.4 ng/mL.The incidence of gastric cancer in C,T,A,and AT group is 90% , 78.6% ,73.3% ,and 50% respectively. The incidence of AT group was significantly lower than that of C group (P < 0. 05). The BrdU labeling index of AT was 10.2 ± 4.7 , and was significantly lower than that of C group( 18.7 ± 5.5, P<0.05) and T,A group (16.0 ± 5. 8 ,15.4 ± 5.2,P<0.05). The apoptosis index of gastric cancer tissues in AT group were 1.71 ±0.41, and were significantly lower than that of C group (0.91 ±0.14) and T,A group (1.19 ± 0.42,1.29 + 0.43,P<0. 05). Conclusions Both in vitro and in viva, combination of taxol with transfection survivin AS-ODN can get synergetic antitumor effect by re-ducing cell proliferation and augmenting apoptosis.This suggests that survivin is an effective target of antitu-mor therapy.
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