摘要
目的研究携带基质金属蛋白酶组织抑制因子-3(TIMP-3)的重组腺病毒(Ad-TIMP-3)对人乳头瘤病毒(HPV)阳性子宫颈癌细胞放疗敏感性的影响。方法采用Ad-TIMP-3感染HeLa-Luc和CaSki细胞,MTT法检测Ad-TIMP-3对HeLa-Luc和CaSki细胞增殖的影响,平板克隆形成实验检测Ad-TIMP-3与X线联合应用对细胞生长能力的影响。将经过不同处理的HeLa-Luc细胞接种于裸鼠腋下,分别观察正常对照组、单独病毒组、单独放射组和联合应用组裸鼠体内肿瘤的生长情况,绘制生长曲线。结果 Ad-TIMP-3能显著抑制HeLa-Luc和CaSki细胞增殖,呈现剂量效应关系。Ad-TIMP-3与X线联合应用可显著减少HeLa-Luc和CaSki细胞平板克隆形成数(P均<0.05)。单独病毒组、单独放射组和联合应用组裸鼠移植瘤重量分别为(0.216±0.098)、(0.276±0.073)和(0.044±0.043)g,均明显低于正常对照组的(0.534±0.218)g(P均<0.05),联合应用组明显低于单独病毒组和单独放射组(P均<0.05)。单独病毒组、单独放射组和联合应用组的抑瘤率分别为59.60%、48.30%和91.80%。结论 Ad-TIMP-3能抑制子宫颈癌细胞增殖,与X线联合应用可显著提高子宫颈癌细胞对放射治疗的敏感性,抑制子宫颈癌细胞体内致瘤能力。
Objective To explore the effects of adenovirus-delivered tissue inhibitor of metalloprotein-ases-3（Ad-TIMP-3）on the irradiation sensitivity of human papillomavirus（HPV）-positive cervical cancer cells.Methods An adenovirus expressing TIMP-3（Ad-TIMP-3）,alone or in combination with irradiation,was used to treat HPV-positive cervical cancer cells HeLa-Luc and CaSki.The effects of Ad-TIMP-3 on the proliferation of HeLa-Luc and CaSki cells were detected with MTT assay.The effect of the combination of Ad-TIMP-3 and X-ray on the proliferation of cells were determined by clone formation assay.Twenty nude mice were equally randomly divided into four groups：normal control group,Ad-TIMP-3 group,X-ray group,and combination group.The size of tumor was measured separately,and tumor growth curves were drawn.Results Ad-TIMP-3 significantly inhibited the proliferation of HPV-positive cervical cancer cells in a dose-dependent manner.Combination of Ad-TIMP-3 and X-ray significantly decreased the clones of HeLa-Luc and CaSki than Ad-TIMP-3 or X-ray alone（P〈0.05）.The tumor weights were（0.216±0.098）,（0.276±0.073）,and（0.044±0.043）g,respectively,in Ad-TIMP-3 group,X-ray group,and combination group,which were all significantly lower than that in normal control group [（0.534±0.218）g]（all P〈0.05）.In addition,the tumor weight in the combination group was significantly lower than that in Ad-TIMP-3 group and X-ray group（both P〈0.05）.The tumor inhibition rate was 59.60%,48.30%,and 91.80% in X-ray group,Ad-TIMP-3 group and combination group,respectively.Conclusions Ad-TIMP-3 can effectively inhibit the proliferation of cervical cancer cells.When combined with X-ray,it can remarkably increase the irradiation sensitivity of HPV-positive cervical cancer cells,and thus suppress the tumorigenesis capability of these cells in vivo.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2010年第5期521-525,共5页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金青年项目(C03030401)
北京市科技新星课题(2006B09)~~
