Cisplatin in combination with Phenethyl Isothiocyanate (PEITC), a potential new therapeutic strategy for malignant pleural mesothelioma.
Cisplatin in combination with Phenethyl Isothiocyanate (PEITC), a potential new therapeutic strategy for malignant pleural mesothelioma.
复制标题
DOI：
10.18632/oncotarget.2604
复制
发表时间：
2014-11-30
期刊：
影响因子：
--
通讯作者：
Blanquart C
中科院分区：
文献类型：
--
作者：
Denis I;Cellerin L;Gregoire M;Blanquart C
恶性胸膜间皮瘤（MPM）是一种非常具有侵袭性的癌症，诊断和预后都很差。MPM的一线治疗是顺铂和培美曲塞的联合治疗，但疗效有限，副作用严重。天然化合物异硫氰酸苯乙酯（PEITC）先前在几种癌细胞系上显示出有趣的抗肿瘤特性。因此，我们的目的是评估PEITC单独使用或与顺铂联合使用以改善MPM治疗。9个MPM细胞系和原代间皮细胞（PMC），分别与MPM微环境中存在的M2巨噬细胞共培养或未共培养，用于评估PEITC和顺铂的抗肿瘤特性。这些化合物可以单独使用，也可以联合使用。PEITC和顺铂对MPM细胞均呈剂量依赖性。我们在此表明，petc诱导的细胞毒性是由于活性氧的产生。此外，我们发现顺铂- peitc联合允许两种化合物的细胞毒性作用的潜在化，并阻止耐药MPM细胞的出现。有趣的是，PMC对该组合不敏感。最后，我们发现M2巨噬细胞并没有改变联合用药的抗肿瘤特性。因此，顺铂- peitc联合代表了一种有希望的策略来诱导对恶性细胞的选择性毒性。
Malignant pleural mesothelioma (MPM) is a very aggressive form of cancer with a poor diagnosis and prognosis. The first line treatment for MPM is a combination of cisplatin and Pemetrexed, which displayed limited efficacy and severe side effects. The naturally occurring compound phenethyl isothiocyanate (PEITC) previously showed interesting anti-tumor properties on several cancer cell lines. We thus aim at evaluating PEITC used alone or in combination with cisplatin in order to improve MPM treatment. Nine MPM cell lines and primary mesothelial cells (PMC), co-cultured or not with M2 macrophages present in MPM microenvironment, were used to assess PEITC and cisplatin anti-tumor properties. Compounds were used alone or in combination. Both PEITC and cisplatin were cytotoxic on MPM cells in a dose dependent manner. We herein showed that PEITC-induced cytotoxicity was due to the generation of reactive oxygen species. Moreover, we showed that cisplatin-PEITC combination allowed the potentialization of both compounds' cytotoxic effects and prevented the emergence of resistant MPM cells. Interestingly, PMC were not sensitive to the combination. Finally, we showed that M2 macrophages did not alter the anti-tumor properties of the combination. Cisplatin-PEITC combination thus represents a promising strategy to induce a selective toxicity towards malignant cells.
登录
查看更多内容
影响因子：
6.7
作者：
Lee, Ji Won;Cho, Min Kyung
通讯作者：
Cho, Min Kyung
影响因子：
3.3
作者：
Martins, N. M.;Santos, N. A. G.;Santos, A. C.
通讯作者：
Santos, A. C.
DOI：
10.1024/0300-9831.72.1.26
发表时间：
2002-01-01
影响因子：
2.3
作者：
Johnson, IT
通讯作者：
Johnson, IT
影响因子：
168.9
作者：
London, SJ;Yuan, JM;Yu, MC
通讯作者：
Yu, MC
影响因子：
4.1
作者：
Di Pasqua, Anthony J.;Hong, Charles;Wu, Mona Y.;McCracken, Erin;Wang, Xiantao;Mi, Lixin;Chung, Fung-Lung
通讯作者：
Chung, Fung-Lung