Trichosanthin enhances sensitivity of non-small cell lung cancer (NSCLC) TRAIL-resistance cells.
Trichosanthin enhances sensitivity of non-small cell lung cancer (NSCLC) TRAIL-resistance cells.
复制标题
天花粉素增强非小细胞肺癌 (NSCLC) TRAIL 耐药细胞的敏感性
DOI：
10.7150/ijbs.22811
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发表时间：
2018
影响因子：
9.2
通讯作者：
Xie C
中科院分区：
文献类型：
--
作者：
You C;Sun Y;Zhang S;Tang G;Zhang N;Li C;Tian X;Ma S;Luo Y;Sun W;Wang F;Liu X;Xiao Y;Gong Y;Zhang J;Xie C
肿瘤坏死因子相关凋亡诱导配体（TRAIL）对多种恶性肿瘤具有特异性抗肿瘤活性。然而，超过一半的肺癌细胞对TRAIL相关药物产生耐药性。天花粉素（TCS）是一种中药，对多种恶性肿瘤具有较强的抑制作用。然而，其在非小细胞肺癌（NSCLC）中对 TRAIL 耐药的作用尚未被揭示。为了研究TCS诱导TRAIL敏感性的分子机制，我们将TCS给予TRAIL耐药的NSCLC细胞，发现TCS和TRAIL联合治疗抑制癌细胞增殖和侵袭，并诱导细胞凋亡和S期阻滞。这种联合治疗方法调节了外源性凋亡相关蛋白 Caspase 3/8 和 PARP 的表达水平；内在凋亡相关蛋白 BCL-2 和 BAX；侵袭相关蛋白 E-钙粘蛋白、N-钙粘蛋白、波形蛋白、ICAM-1、MMP-2 和 MMP-9；以及细胞周期相关蛋白 P27、CCNE1 和 CDK2。在联合治疗中还观察到细胞表面死亡受体（DR）的表达上调和重新分布。总之，我们的结果表明，TCS 通过上调和重新分布 DR4 和 DR5、诱导细胞凋亡、调节侵袭和细胞周期相关蛋白来使 NSCLC 细胞对 TRAIL 敏感。我们的结果提供了一种增强 TRAIL 敏感性的潜在治疗方法。
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has a specific antitumour activity against many malignant tumours. However, more than half of lung cancer cells are resistant to TRAIL-relevant drugs. Trichosanthin (TCS) is a traditional Chinese medicine with strong inhibitive effects on various malignancies. Nevertheless, its function on TRAIL resistance has not been revealed in non-small cell lung cancer (NSCLC). To examine the molecular mechanisms of TCS-induced TRAIL sensitivity, we administrated TCS to TRAIL-resistance NSCLC cells, and found that the combination treatment of TCS and TRAIL inhibited cancer cell proliferation and invasion, and induced cell apoptosis and S-phase arrest. This combined therapeutic method regulated the expression levels of extrinsic apoptosis-associated proteins Caspase 3/8 and PARP; intrinsic apoptosis-associated proteins BCL-2 and BAX; invasion-associated proteins E-cadherin, N-cadherin, Vimentin, ICAM-1, MMP-2 and MMP-9; and cell cycle-associated proteins P27, CCNE1 and CDK2. Up-expression and redistribution of death receptors (DRs) on the cell surface were also observed in combined treatment. In conclusion, our results indicated that TCS rendered NSCLC cells sensitivity to TRAIL via upregulating and redistributing DR4 and DR5, inducing apoptosis, and regulating invasion and cell cycle related proteins. Our results provided a potential therapeutic method to enhance TRAIL-sensitivity.
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影响因子：
1.6
作者：
Bhatia, N;McDonald, KA;Dandekar, AM
通讯作者：
Dandekar, AM
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：
3.4
作者：
Liu, Fenye;Wang, Bing;Yu, Shudong
通讯作者：
Yu, Shudong
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：
5.3
作者：
Greco, F. Anthony;Bonomi, Philip;Klein, Jerry
通讯作者：
Klein, Jerry