Research on the Impact of TRAIL on Apoptosis of SKOV3 Cell Line Ovarian Tumor Xenografts in Nude Mice_West China Medical Journal

Authors：

LI Chunmei ¹ , PENG Zhilan ¹ , YANG Kaixuan ² , LIU Ying ² , HUANG Qin ²

1. Department of Gynecology and Obstetrics; 2. Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

Keywords：

卵巢癌; 肿瘤坏死因子相关凋亡诱导配体; 末端脱氧核苷酸转移酶介导核苷酸缺口标记技术; 半胱天冬氨酸蛋白酶-3; 凋亡; 小鼠

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

【摘要】　目的　研究肿瘤坏死因子相关凋亡诱导配体（TRAIL）蛋白对SKOV3移植瘤细胞半胱天冬氨酸蛋白酶-3（Caspase-3）表达的影响及其与肿瘤细胞凋亡的关系。　方法　建立雌性裸小鼠SKOV3移植瘤24只，随机分为4组，每组6只。TRAIL组单用重组人TRAIL蛋白（10 μg/kg），顺铂（DDP）组单用DDP（3 mg/kg），TRAIL+DDP组联合使用TRAIL蛋白（10 μg/kg）和DDP（3 mg/kg），空白对照组给予0.5 mL生理盐水。经处理后，各组的组织切片用免疫组织化学染色检测Caspase-3的表达和末端脱氧核苷酸转移酶介导核苷酸缺口标记技术（TUNEL）检测肿瘤细胞凋亡指数。　结果　 Caspase-3的表达水平在TRAIL组（171.67±14.38）、DDP组（172.50±14.75）、联合组（230.00±40.99）中均明显高于对照组（135.83±16.25）（P lt;0.05）。SKOV3移植瘤细胞凋亡指数在空白对照组、TRAIL组、DDP组和联合组分别为16.67±5.43、33.17±8.42、24.33±4.59和40.50±6.16，TRAIL组和联合组细胞凋亡指数较空白对照组和DDP组明显增高（P lt;0.05）。　结论　 TRAIL蛋白使卵巢癌移植瘤细胞的Caspase-3表达增强，TRAIL蛋白促进肿瘤细胞凋亡发生。
【Abstract】　Objective　 To investigate the effects of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the expression of Cysteine/aspartic acid specific protease- 3 (Caspase-3) in SKOV3 ovarian tumor cells and its relationship with the apoptosis of the ovarian tumor xenografts in nude mice. 　Methods　 Twenty-four nude mice with SKOV3 cell line ovarian tumor were randomly divided into four groups with 6 in each group. TRAIL (10 μg/kg) was given to the mice in the TRAIL group; DDP (3 μg/kg) was given to the mice in the DDP group; TRAIL (10 μg/kg) and DDP (3 μg/kg) were given to the mice in the TRAIL+DDP group; and 0.5 mL of saline solution was give to the mice in the control group. The expression of Caspase-3 was detected with immunohistochemistry. The apoptosis index (AI) of cells was determined by Terminal deoxynucleotidyl transferase mediated-dUTP nick end labeling (TUNEL).　Results　 The expression of Caspase-3 in the TRAIL group (171.67±14.38), DDP group (172.50±14.75), and TRAIL+DDP group (230.00±40.99) was significantly higher than that in the control group (135.83±16.25) (P lt;0.05). The apoptosis index for the control group, TRAIL group, DDP group and TRAIL+DDP group was 16.67±5.43, 33.17±8.42, 24.33±4.59, and 40.50±6.16, respectively. The apoptosis index for the TRAIL group and the TRAIL+DDP group was significantly higher than that in the control group and the DDP group (P lt;0.05).　Conclusion　 Soluble TRAIL has an effect on enhancing the expression of Caspase-3 in implanted tumor in nude mice. TRAIL protein can inhibit the growth of SKOV3 cells in nude mice by inducing cell apoptosis.

Citation： LI Chunmei,PENG Zhilan,YANG Kaixuan,LIU Ying,HUANG Qin. Research on the Impact of TRAIL on Apoptosis of SKOV3 Cell Line Ovarian Tumor Xenografts in Nude Mice. West China Medical Journal, 2011, 26(4): 481-484. doi: Copy

1.	Cretney E, Takeda K, Yagita H, et al. Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice[J]. J Immunol, 2002, 168(3): 1356-1361.
2.	MeKay TR, Bell S, Tenev T, et al. Procaspase 3 expression in ovarian carcinoma cells increases survivin transcription which can be countered with a dominant-negative mutant, survivin T34A; a combination gene therapy strategy[J].Oncogene, 2003, 22(23): 3539-3547.
3.	李春梅, 彭芝兰, 尹如铁, 等. TRAIL对人卵巢癌SKOV3细胞生长及凋亡的影响[J]. 四川大学学报(医学版), 2006, 37(5): 761-764.
4.	Kischkel FC, Lawrence DA, Chuntharapai A, et al. Apo2L/ TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5[J]. Immunity, 2000, 12(6): 611-620.
5.	Lin ML, Lu YC, Chung JG, et al. Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway[J]. Cancer Lett, 2010, 291(1): 46-58.
6.	Jin H, Yang R, Fong S, et al. Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand cooperates with chemotherapy to inhibit orthotopic lung tumor growth and improve survival[J]. Cancer Res, 2004, 64(14): 4900-4905.
7.	Shankar S, Singh TR, Chen X, et al. The sequential treatment with ionizing radiation followed by TRAIL/Apo-2L reduces tumor growth and induces apoptosis of breast tumor xenografts in nude mice[J]. Int J Oncol, 2004, 24(5): 1133-1140.
8.	Bellail AC, Qi L, Mulligan P, et al. TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges[J]. Rev Recent Clin Trials, 2009, 4(1): 34-41.
9.	Takeda K, Yamaguchi N, Akiba H, et al. Induction of tumor-specific T cell immunity by anti-dr5 antibody therapy[J]. J Exp Med, 2004, 199(4): 437-448.
10.	Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy[J]. Nat Rev Cancer, 2008, 8(10): 782-798.
11.	El-Gazzar A, Perco P, Eckelhart E, et al. Natural immunity enhances the activity of a DR5 agonistic antibody and carboplatin in the treatment of ovarian cancer[J]. Mol Cancer Ther, 2010, 9(4): 1007-1018.
12.	李春梅, 彭芝兰, 尹如铁. TRAIL蛋白与顺铂联合应用对卵巢癌裸鼠腹腔移植瘤的生长抑制作用[J]. 中华妇产科杂志, 2006, 41(8): 568-556.
13.	Gliniak B, Le T. Tumor necrosis factor-related apoptosis-inducing ligand’s antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11[J]. Cancer Res, 1999, 59(24): 6153-6158.
14.	Nagane M, Pan G, Weddle J, et al. Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo[J]. Cancer Res, 2000, 60(4): 847-853.

1. 　Cretney E, Takeda K, Yagita H, et al. Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice[J]. J Immunol, 2002, 168(3): 1356-1361.
2. 　MeKay TR, Bell S, Tenev T, et al. Procaspase 3 expression in ovarian carcinoma cells increases survivin transcription which can be countered with a dominant-negative mutant, survivin T34A; a combination gene therapy strategy[J].Oncogene, 2003, 22(23): 3539-3547.
3. 　李春梅, 彭芝兰, 尹如铁, 等. TRAIL对人卵巢癌SKOV3细胞生长及凋亡的影响[J]. 四川大学学报(医学版), 2006, 37(5): 761-764.
4. 　Kischkel FC, Lawrence DA, Chuntharapai A, et al. Apo2L/ TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5[J]. Immunity, 2000, 12(6): 611-620.
5. 　Lin ML, Lu YC, Chung JG, et al. Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway[J]. Cancer Lett, 2010, 291(1): 46-58.
6. 　Jin H, Yang R, Fong S, et al. Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand cooperates with chemotherapy to inhibit orthotopic lung tumor growth and improve survival[J]. Cancer Res, 2004, 64(14): 4900-4905.
7. 　Shankar S, Singh TR, Chen X, et al. The sequential treatment with ionizing radiation followed by TRAIL/Apo-2L reduces tumor growth and induces apoptosis of breast tumor xenografts in nude mice[J]. Int J Oncol, 2004, 24(5): 1133-1140.
8. 　Bellail AC, Qi L, Mulligan P, et al. TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges[J]. Rev Recent Clin Trials, 2009, 4(1): 34-41.
9. 　Takeda K, Yamaguchi N, Akiba H, et al. Induction of tumor-specific T cell immunity by anti-dr5 antibody therapy[J]. J Exp Med, 2004, 199(4): 437-448.
10. 　Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy[J]. Nat Rev Cancer, 2008, 8(10): 782-798.
11. 　El-Gazzar A, Perco P, Eckelhart E, et al. Natural immunity enhances the activity of a DR5 agonistic antibody and carboplatin in the treatment of ovarian cancer[J]. Mol Cancer Ther, 2010, 9(4): 1007-1018.
12. 　李春梅, 彭芝兰, 尹如铁. TRAIL蛋白与顺铂联合应用对卵巢癌裸鼠腹腔移植瘤的生长抑制作用[J]. 中华妇产科杂志, 2006, 41(8): 568-556.
13. 　Gliniak B, Le T. Tumor necrosis factor-related apoptosis-inducing ligand’s antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11[J]. Cancer Res, 1999, 59(24): 6153-6158.
14. 　Nagane M, Pan G, Weddle J, et al. Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo[J]. Cancer Res, 2000, 60(4): 847-853.

West China Medical Journal

Research on the Impact of TRAIL on Apoptosis of SKOV3 Cell Line Ovarian Tumor Xenografts in Nude Mice

Abstract Full text Figures/Tables Video References Cited by

Format

Content