Trichosanthin cooperates with Granzyme B to restrain tumor formation in tongue squamous cell carcinoma.
Trichosanthin cooperates with Granzyme B to restrain tumor formation in tongue squamous cell carcinoma.
复制标题
天花粉素与颗粒酶B协同抑制舌鳞状细胞癌肿瘤形成
DOI：
10.1186/s12906-021-03266-6
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发表时间：
2021-03-09
影响因子：
3.9
通讯作者：
Sha O
中科院分区：
文献类型：
--
作者：
Zhu Z;Ying Z;Zeng M;Zhang Q;Liao G;Liang Y;Li C;Zhang C;Wang X;Jiang W;Luan P;Sha O
研究背景舌癌是一种常见的口腔癌类型，预后较差，治疗后生存率较低。治疗TSCC的各种策略和新药正在涌现和研究中。天花粉蛋白(Trichosantin，TCS)是从天花粉的块根中提取的，具有多种生物学和药理作用，包括抑制癌细胞生长。颗粒酶B(GrzB)是一种由自然杀伤细胞和细胞毒性T细胞分泌的常见毒性蛋白。我们小组已经报道，TCS联合GrzB可能是抑制肝肿瘤进展的更好方法，但与使用该联合治疗TSCC相关的数据仍然有限。本研究的目的是探讨天花粉蛋白对舌鳞状细胞癌过程的影响及其机制。方法首先，我们利用两种类型的鳞癌细胞系筛选天花粉蛋白的潜在抗肿瘤活性。随后，建立了裸鼠皮下鳞状细胞癌移植瘤模型。将模型小鼠随机分为4组：对照组、TCS治疗组、GrzB治疗组、TCS/GrzB联合治疗组。采用Ki67、增殖细胞核抗原、半胱氨酸天冬氨酸氨基转移酶-3、Bcl-2、VEGFA等多种致瘤指标，观察不同治疗方法对肿瘤生长的影响。与对照组相比，TCS或GrzB治疗显著抑制肿瘤生长。TCS/GrzB组合对肿瘤生长的抑制作用强于任何一种药物。TCS通过下调Ki67和Bcl2蛋白表达，促进肿瘤细胞凋亡，从而抑制肿瘤增殖。TCS/GrzB联合用药组与单独用药组相比，Ki67表达进一步下调，caspase-3活化水平升高。结论TCS/GrzB联合用药可作为一种有效的免疫治疗方法。
BackgroundTongue squamous cell carcinoma (TSCC) is a common type of oral cancer, with a relatively poor prognosis and low post-treatment survival rate. Various strategies and novel drugs to treat TSCC are emerging and under investigation. Trichosanthin (TCS), extracted from the root tubers of Tian-Hua-Fen, has been found to have multiple biological and pharmacological functions, including inhibiting the growth of cancer cells. Granzyme B (GrzB) is a common toxic protein secreted by natural killer cells and cytotoxic T cells. Our group has reported that TCS combined with GrzB might be a superior approach to inhibit liver tumor progression, but data relating to the use of this combination to treat TSCC remain limited. The aim of this study was to examine the effectiveness of TCS on TSCC processes and underlying mechanisms.MethodsFirst, we screened the potential antitumor activity of TCS using two types of SCC cell lines. Subsequently, a subcutaneous squamous cell carcinoma xenograft model in nude mice was established. These model mice were randomly divided into four groups and treated as follows: control group, TCS treatment group, GrzB treatment group, and TCS/GrzB combination treatment group. Various tumorigenesis parameters, such as Ki67, PCNA, caspase-3, Bcl-2 and VEGFA, et al., were performed to determine the effects of these treatments on tumor development.ResultsScreening confirmed that the SCC25 line exhibited greater sensitivity than the SCC15 line to TCS in vitro studies. TCS or GrzB treatment significantly inhibited tumor growth compared with the inhibition seen in the control group. The TCS/GrzB combination inhibited tumor growth more than either drug alone. TCS treatment inhibited tumor proliferation by downregulating Ki67 and Bcl2 protein expression while accelerating tumor apoptosis. In the TCS/GrzB-treated group, expression of Ki67 was further downregulated, while the level of activated caspase-3 was increased, compared with their expression in either of the single drug treatment groups.ConclusionThese results suggest that the TCS/GrzB combination could represent an effective immunotherapy for TSCC.
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影响因子：
2.8
作者：
Chen, Yali;Han, Ling;Zheng, Ai
通讯作者：
Zheng, Ai
DOI：
10.1016/j.bbrc.2012.11.080
发表时间：
2013-01-11
影响因子：
3.1
作者：
He, Dongxu;Jin, Jian;Ma, Xin
通讯作者：
Ma, Xin
影响因子：
--
作者：
Li C;Zeng M;Chi H;Shen J;Ng TB;Jin G;Lu D;Fan X;Xiong B;Xiao Z;Sha O
通讯作者：
Sha O
DOI：
10.1002/ar.21142
发表时间：
2010-06-01
影响因子：
2
作者：
Li, Meng;Li, Xiang;Li, Ji-Cheng
通讯作者：
Li, Ji-Cheng
影响因子：
2.1
作者：
Le Campion ACOV;Ribeiro CMB;Luiz RR;da Silva Júnior FF;Barros HCS;Dos Santos KCB;Ferreira SJ;Gonçalves LS;Ferreira SMS
通讯作者：
Ferreira SMS