Mitomycin C induces bystander killing in homogeneous and heterogeneous hepatoma cellular models.
Mitomycin C induces bystander killing in homogeneous and heterogeneous hepatoma cellular models.
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丝裂霉素C在同质和异质肝癌细胞模型中诱导旁观者杀死。
DOI：
10.1186/1476-4598-8-87
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发表时间：
2009-10-21
期刊：
影响因子：
37.3
通讯作者：
Bhat MK
中科院分区：
文献类型：
--
作者：
Kumari R;Sharma A;Ajay AK;Bhat MK
肝细胞癌（HCC）是世界上最常见的癌症之一，对化疗特别难治。一些研究建议联合化疗方案治疗HCC。然而，这些治疗方法在肝癌患者的肿瘤消退和延长生存期方面效果不明显。因此，迫切需要开发更有效的治疗工具和治疗HCC的新策略。在过去的十年中，“旁观者效应”作为治疗某些人类肿瘤的一种可能的治疗策略受到了广泛的关注。对这种治疗方法的兴趣源于许多描述辐射诱导的旁观者效应的报告。然而，对化疗诱导的旁观者效应的认识仍然有限。因此，利用丝裂霉素C （Mitomycin C， MMC）探讨化疗诱导肝癌细胞的旁观者现象。MMC诱导的旁观者杀伤仅在肝癌细胞中观察到，而在宫颈癌细胞中没有发生。MMC诱导的旁观者杀戮可通过介质转移。它发生在共培养的细胞中，表明分泌因子和膜结合因子的参与。在处理细胞的条件培养基中检测到FasL和TRAIL。在中等转移实验中，用EDTA（一种广谱蛋白酶抑制剂）预处理可以减少MMC诱导的旁观者死亡。药物暴露后，Fas和TRAIL受体的表达增加，用FasL和TRAIL的中和抗体治疗可抑制旁观者的杀伤。我们的研究结果强调了MMC在HCC治疗中的重要性，并暗示了膜结合和分泌形式的FasL和TRAIL在MMC诱导的旁观者杀伤中的作用。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide that is particularly refractory to chemotherapy. Several studies have proposed combination chemotherapy regimen for HCC treatment. However, these therapies are not effective in regressing tumor and prolonging survival of patient's suffering from HCC. Therefore, the development of more effective therapeutic tools and new strategies for the treatment of HCC are urgently needed. Over the last decade much attention has been focused on "bystander effect" as a possible therapeutic strategy for the treatment of certain human tumors. Interest in this therapeutic approach originated from numerous reports describing the radiation induced bystander effect. However, the knowledge about chemotherapy induced bystander effect is still limited. Hence, chemotherapy induced bystander phenomenon in hepatoma cells was explored by utilizing Mitomycin C (MMC). MMC induced bystander killing was observed only in hepatoma cells and it did not occur in cervical cancer cells. MMC induced bystander killing was transferable via medium. It occurred in co-cultured cells indicating the involvement of secreted as well as membrane bound factors. FasL and TRAIL were detected in the conditioned medium from treated cells. In medium transfer experiment, pre-treatment with EDTA (a broad range protease inhibitor) diminished MMC induced bystander killing. Following drug exposure, expression of Fas and TRAIL receptors increased and treatment with neutralizing antibodies against FasL and TRAIL inhibited bystander killing. Our results highlight the therapeutic importance of MMC in the treatment of HCC and implicate role of membrane bound and secreted forms of FasL and TRAIL in MMC induced bystander killing.
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DOI：
10.1084/jem.189.2.441
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Afford SC;Randhawa S;Eliopoulos AG;Hubscher SG;Young LS;Adams DH
通讯作者：
Adams DH
影响因子：
8.8
作者：
Chen, S.;Zhao, Y.;Han, W.;Zhao, G.;Zhu, L.;Wang, J.;Bao, L.;Jiang, E.;Xu, A.;Hei, T. K.;Yu, Z.;Wu, L.
通讯作者：
Wu, L.
影响因子：
9.7
作者：
Kang, Yun Hee;Lee, Kyung-Ae;Yoon, Do-Young
通讯作者：
Yoon, Do-Young
FASL和FAS的细胞外结构域足以形成高稳定性的超分子FASL-FAS簇。
影响因子：
7.8
作者：
Henkler, Frank;Behrle, Eva;Dennehy, Kevin M;Wicovsky, Andreas;Peters, Nathalie;Warnke, Clemens;Pfizenmaier, Klaus;Wajant, Harald
通讯作者：
Wajant, Harald
DOI：
10.1073/pnas.011417098
发表时间：
2001-01-16
影响因子：
11.1
作者：
Azzam, EI;de Toledo, SM;Little, JB
通讯作者：
Little, JB