Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma.
Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma.
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反义寡核苷酸与全反式维A酸对口腔鳞癌具有协同抗肿瘤作用
DOI：
10.1186/1471-2407-8-159
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发表时间：
2008-06-03
期刊：
影响因子：
3.8
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Xu Q;Zhang Z;Zhang P;Chen W
抗hTR的反义寡核苷酸（as - odn -hTR）作为多种人类恶性肿瘤的治疗策略已显示出良好的效果。全反式维甲酸（All-trans retinoic acid， ATRA）是一种在细胞分化和凋亡过程中起重要作用的信号分子。ATRA的生物反应目前用于治疗各种人类癌症。本研究的目的是评估As-ODN-hTR联合ATRA的体内抗肿瘤作用。方法皮下注射Tca8113细胞建立人口腔鳞状细胞癌原位模型。小鼠分别用抗hTR的寡核苷酸（S-ODN-hTR）单独、As-ODN-hTR单独、ATRA单独、As-ODN-hTR + ATRA或S-ODN-hTR + ATRA)处理。评估小鼠的肿瘤大小和重量。采用TRAP法检测端粒酶活性，Tunel法检测凋亡细胞，免疫组化法检测凋亡相关蛋白（Bcl-2、Bax）表达，并检测肿瘤标本超微结构形态学变化。结果As-ODN-hTR和ATRA均能显著抑制OSCC异种移植实体瘤模型的肿瘤生长，且两者联用具有协同抗肿瘤作用。我们还证明了这种抗肿瘤作用与端粒酶活性的抑制有关。此外，在处理组织中观察到凋亡细胞数量显著增加，典型的凋亡形态和抗凋亡蛋白bcl-2的下调。结论As-ODN-hTR与ATRA联合使用具有协同抗肿瘤作用。这种抗肿瘤作用主要与端粒酶活性降低引起细胞凋亡有关。Bcl-2在这一过程中起着重要作用。因此，As-ODN-hTR联合ATRA可能是治疗人口腔鳞状细胞癌的一种途径。
BackgroundAntisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo.MethodsIn situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined.ResultsBoth As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues.ConclusionThe combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma.
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影响因子：
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作者：
Gurova, KV;Gudkov, AV
通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/j.ijom.2005.11.004
发表时间：
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影响因子：
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作者：
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