当前位置: X-MOL 学术Int. J. Med. Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma
International Journal of Medical Sciences ( IF 3.2 ) Pub Date : 2021-7-11 , DOI: 10.7150/ijms.61944
Wenshuang Wu 1, 2 , Tao Wei 1 , ZhiHui Li 1, 2 , Jingqiang Zhu 1
Affiliation  

A functional p53 protein plays an important role in killing tumor cells. Previous studies showed that chemotherapeutic drug, paclitaxel (PTX), showed anti-tumor activity through inducing G2/M arrest and apoptosis by targeting microtubules in tumor cells. However, PTX was not sensitive to p53-inactivated papillary thyroid carcinoma (PTC) cells by inducing G2/M arrest only. Recombinant adenovirus-p53 (rAd-p53) was used to increase the level of p53, which significantly increased the sensitivity of PTC cells to PTX by inducing S arrest, G2/M arrest and apoptosis. To discuss the anti-tumor mechanism of rAd-p53 + PTX and found p53 activation was necessary for anti-tumor effect of PTX in PTC cells. There was high level of p53 in rAd-p53-treated PTC cells. rAd-p53 + PTX increased the level of p21, p-ATM and γ-H2AX and decreased the level of Cyclin D1/E1, suggesting p53 activated p21 which negatively regulated cyclins to induce S arrest response to DNA damage in PTC cells. rAd-p53 + PTX increased the levels of cleaved-PARP-1, cleaved -Caspase 3, and BAX and decreased the level of BCL-XL, suggesting p53 regulates the expression of BAX/BCL-XL to mediate DNA damage-induced apoptosis in PTC cells. Furthermore, rAd-p53 + PTX showed significant tumor inhibition in TPC-1 xenograft model, with an inhibitory rate of 79.39%. TUNEL assay showed rAd-p53 + PTX induced notable apoptosis in tumor tissues. rAd-p53 showed good sensitization of PTX in vitro and in vivo through inducing DNA damage induced-apoptosis indicated p53-dependent apoptosis was essential for the antitumor effect of PTX in PTC.

中文翻译:

p53依赖性细胞凋亡对于紫杉醇对甲状腺乳头状癌DNA损伤反应的抗肿瘤作用至关重要

功能性 p53 蛋白在杀死肿瘤细胞中起重要作用。先前的研究表明,化疗药物紫杉醇 (PTX) 通过靶向肿瘤细胞中的微管诱导 G2/M 期阻滞和细胞凋亡,从而显示出抗肿瘤活性。然而,PTX 仅通过诱导 G2/M 期阻滞对 p53 灭活的甲状腺乳头状癌 (PTC) 细胞不敏感。重组腺病毒-p53(rAd-p53)用于增加p53的水平,通过诱导S期阻滞、G2/M期阻滞和凋亡显着增加PTC细胞对PTX的敏感性。讨论rAd-p53 + PTX的抗肿瘤机制,发现p53激活是PTX在PTC细胞中的抗肿瘤作用所必需的。在 rAd-p53 处理的 PTC 细胞中存在高水平的 p53。rAd-p53 + PTX 增加了 p21、p-ATM 和 γ-H2AX 的水平,降低了 Cyclin D1/E1 的水平,表明 p53 激活 p21,其负调节细胞周期蛋白以诱导对 PTC 细胞中 DNA 损伤的 S 阻滞反应。rAd-p53 + PTX 增加了 cleaved-PARP-1、cleaved -Caspase 3 和 BAX 的水平并降低了 BCL-XL 的水平,表明 p53 调节 BAX/BCL-XL 的表达以介导 DNA 损伤诱导的细胞凋亡PTC 细胞。此外,rAd-p53 + PTX 在 TPC-1 异种移植模型中表现出显着的肿瘤抑制作用,抑制率为 79.39%。TUNEL 分析显示 rAd-p53 + PTX 在肿瘤组织中诱导了显着的细胞凋亡。rAd-p53 对 PTX 表现出良好的致敏性 提示 p53 调节 BAX/BCL-XL 的表达以介导 PTC 细胞中 DNA 损伤诱导的细胞凋亡。此外,rAd-p53 + PTX 在 TPC-1 异种移植模型中表现出显着的肿瘤抑制作用,抑制率为 79.39%。TUNEL 分析显示 rAd-p53 + PTX 在肿瘤组织中诱导了显着的细胞凋亡。rAd-p53 对 PTX 表现出良好的致敏性 提示 p53 调节 BAX/BCL-XL 的表达以介导 PTC 细胞中 DNA 损伤诱导的细胞凋亡。此外,rAd-p53 + PTX 在 TPC-1 异种移植模型中表现出显着的肿瘤抑制作用,抑制率为 79.39%。TUNEL 分析显示 rAd-p53 + PTX 在肿瘤组织中诱导了显着的细胞凋亡。rAd-p53 对 PTX 表现出良好的致敏性在体外体内通过诱导DNA损伤诱导细胞凋亡表明p53依赖性细胞凋亡对于PTX在PTC中的抗肿瘤作用是必不可少的。
更新日期:2021-09-08
down
wechat
bug