1整合素反义寡核苷酸联合顺铂 治疗人卵巢癌裸鼠移植瘤的研究

马玲; 田敏

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1整合素反义寡核苷酸联合顺铂治疗人卵巢癌裸鼠移植瘤的研究

马玲 , 田敏

文章导航 > 蚌埠医学院学报 > 2014, 38 > 4: (433-437)

引用本文:

Citation:

1整合素反义寡核苷酸联合顺铂治疗人卵巢癌裸鼠移植瘤的研究

马玲¹,
田敏²

1.
1. 蚌埠医学院第一附属医院肿瘤妇科, 安徽蚌埠 233004;
2.
2. 安徽省淮南市妇幼保健院妇产科, 232007

作者简介: 马玲(1970-)，女，副教授，主任医师.

基金项目:
安徽省教育厅自然科学研究资助项目(2006jq1181)

Experimental study of 1integrin antisense oligodeonucleotide in combination with cisplatin for human ovarian carcinoma xenograft in nude mice

MA Ling¹,
TIAN Min²

1.
1. Department of Tumor Gynecological, The First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004；;
2.
2. Huainan Maternity and Child Health Care Hospital, Huainan Anhui 232007, China

摘要: 目的：探讨以1整合素反义寡核苷酸(ASODN)治疗人卵巢癌裸鼠皮下移植瘤的可行性。方法：常规体外培养SKOV3细胞，采用皮下注射法建立移植瘤裸鼠动物模型。32只荷瘤鼠随机分为ASODN组(A组)、ASODN联合顺铂(DDP)组(A+D组)、DDP组和0.9%氯化钠注射液对照组(NS组),每组8只，分组给药。以脂质体包裹的1整合素ASODN直接移植瘤内注射，观察肿瘤生长情况，测瘤体积并计算抑瘤率。采用反转录-聚合酶链反应(RT-PCR)和免疫组织化学方法分别检测1整合素mRNA的表达。结果：A组肿瘤体积和抑瘤率分别为(316.1021.77)mm3和48.15%，与NS组比较抑瘤率较高，肿瘤生长缓慢(P0.01)。而A+D组肿瘤体积和抑瘤率分别为(178.7040.67)mm3和70.37%，与DDP组、A组及NS组差异均有统计学意义(P0.05～P0.01)。RT-PCR和免疫组织化学检测，A组和A+D组肿瘤组织中1整合素mRNA的表达均明显下调(P0.01)。结论：单用1整合素ASDON或联用DDP均可有效抑制人卵巢癌裸鼠皮下移植瘤组织的生长，可能与其特异性下调1整合素基因表达有关。特异性靶向1整合素ASODN可用于卵巢癌的辅助治疗。
- 卵巢肿瘤 /
- 反义寡核苷酸 /
- 1整合素
Abstract: Objective:To explore the feasibility of antisense oligodeoxynucleotide(ASODN) targeting 1integrin gene for treatment of human ovarian cancer in nude mice.Methods:Routinely cultured SKOV3 cells were subcutaneously implanted in the nude mice to establish xenograft animal model.The 32 tumor-bearing mice were randomly divided into ASODN group(A group),ASODN combined with DDP group(A+D group),DDP group and physiological saline control group(NS group)(n=8 in each ).Drug treatment was started after randomization.After 1integrin ASODN mediated by cytofectin was directly injected into the xenograft,the volume and weight of the tumor mass were detected,and then the tumor growth inhibitory rate was calculated.Reverse transcription-polymerase chain reaction(RT-PCR) and immunochemohistology assay were used to detect the expression level of 1integrin mRNA.Results:In the A group,the tumor volume and tumor anticancer efficacy were(316.1021.77) mm3 and 48.15%,respectively.The tumor growth inhibitory rate and tumor volume were significantly different between the NS group and the A group(P0.01).In the A+D group,the tumor volume reduced to (178.7040.67)mm3 and the tumor anticancer efficacy was enhanced to 70.37%,which were significantly different compared with those of the DDP group and other controls(P0.05 to P0.01).Significant down-regulation of 1integrin mRNA expression in the tumor tissues of the A group and A+D group was detected by RT-PCR and immunochemohistology assay(P0.01).Conclusions:Singly use of 1integrin ASODN or combined with DDP can effectively inhibit the growth of human ovarian carcinoma xenograft in nude mice by direct intra-tumoral injection.The anticancer efficacy may be associated with the down regulation of 1integrin expression.ASODN targeting 1integrin gene can be a supportive therapy to the ovarian cancer.
- ovarian neoplasms /
- antisense oligodeoxynucleotide /
- 1 integrin

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1整合素反义寡核苷酸联合顺铂治疗人卵巢癌裸鼠移植瘤的研究

马玲¹
田敏²

作者简介: 马玲(1970-)，女，副教授，主任医师.

1. 1. 蚌埠医学院第一附属医院肿瘤妇科, 安徽蚌埠 233004;
2. 2. 安徽省淮南市妇幼保健院妇产科, 232007

收稿日期: 2012-12-24
网络出版日期: 2014-04-15

基金项目: 安徽省教育厅自然科学研究资助项目(2006jq1181)

关键词:

摘要: 目的：探讨以1整合素反义寡核苷酸(ASODN)治疗人卵巢癌裸鼠皮下移植瘤的可行性。方法：常规体外培养SKOV3细胞，采用皮下注射法建立移植瘤裸鼠动物模型。32只荷瘤鼠随机分为ASODN组(A组)、ASODN联合顺铂(DDP)组(A+D组)、DDP组和0.9%氯化钠注射液对照组(NS组),每组8只，分组给药。以脂质体包裹的1整合素ASODN直接移植瘤内注射，观察肿瘤生长情况，测瘤体积并计算抑瘤率。采用反转录-聚合酶链反应(RT-PCR)和免疫组织化学方法分别检测1整合素mRNA的表达。结果：A组肿瘤体积和抑瘤率分别为(316.1021.77)mm3和48.15%，与NS组比较抑瘤率较高，肿瘤生长缓慢(P0.01)。而A+D组肿瘤体积和抑瘤率分别为(178.7040.67)mm3和70.37%，与DDP组、A组及NS组差异均有统计学意义(P0.05～P0.01)。RT-PCR和免疫组织化学检测，A组和A+D组肿瘤组织中1整合素mRNA的表达均明显下调(P0.01)。结论：单用1整合素ASDON或联用DDP均可有效抑制人卵巢癌裸鼠皮下移植瘤组织的生长，可能与其特异性下调1整合素基因表达有关。特异性靶向1整合素ASODN可用于卵巢癌的辅助治疗。

English Abstract

Experimental study of 1integrin antisense oligodeonucleotide in combination with cisplatin for human ovarian carcinoma xenograft in nude mice

MA Ling¹
TIAN Min²

1. 1. Department of Tumor Gynecological, The First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004；;
2. 2. Huainan Maternity and Child Health Care Hospital, Huainan Anhui 232007, China

Received Date: 2012-12-24
Available Online: 2014-04-15

Abstract: Objective:To explore the feasibility of antisense oligodeoxynucleotide(ASODN) targeting 1integrin gene for treatment of human ovarian cancer in nude mice.Methods:Routinely cultured SKOV3 cells were subcutaneously implanted in the nude mice to establish xenograft animal model.The 32 tumor-bearing mice were randomly divided into ASODN group(A group),ASODN combined with DDP group(A+D group),DDP group and physiological saline control group(NS group)(n=8 in each ).Drug treatment was started after randomization.After 1integrin ASODN mediated by cytofectin was directly injected into the xenograft,the volume and weight of the tumor mass were detected,and then the tumor growth inhibitory rate was calculated.Reverse transcription-polymerase chain reaction(RT-PCR) and immunochemohistology assay were used to detect the expression level of 1integrin mRNA.Results:In the A group,the tumor volume and tumor anticancer efficacy were(316.1021.77) mm3 and 48.15%,respectively.The tumor growth inhibitory rate and tumor volume were significantly different between the NS group and the A group(P0.01).In the A+D group,the tumor volume reduced to (178.7040.67)mm3 and the tumor anticancer efficacy was enhanced to 70.37%,which were significantly different compared with those of the DDP group and other controls(P0.05 to P0.01).Significant down-regulation of 1integrin mRNA expression in the tumor tissues of the A group and A+D group was detected by RT-PCR and immunochemohistology assay(P0.01).Conclusions:Singly use of 1integrin ASODN or combined with DDP can effectively inhibit the growth of human ovarian carcinoma xenograft in nude mice by direct intra-tumoral injection.The anticancer efficacy may be associated with the down regulation of 1integrin expression.ASODN targeting 1integrin gene can be a supportive therapy to the ovarian cancer.