Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor.
Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor.
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DOI：
10.1007/s00280-015-2751-6
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发表时间：
2015-06
影响因子：
3
通讯作者：
Carr, Brian Irving
中科院分区：
文献类型：
--
作者：
D'Alessandro, Rosalba;Refolo, Maria Grazia;Lippolis, Catia;Carella, Nicola;Messa, Caterina;Cavallini, Aldo;Carr, Brian Irving
血小板数与几种肿瘤类型的生长和侵袭性有关，包括肝细胞癌。我们先前发现，血小板裂解物(HPLS)也能刺激生长和迁移，并拮抗两种多激酶抑制剂索拉非尼和雷戈拉非尼对三种肝癌细胞系的生长抑制和凋亡作用。本研究考察了人表皮生长因子(EGF)与索拉非尼或雷戈非尼合用前后的体外功能。用酶联免疫吸附试验试剂盒检测HPLS中EGF的浓度。用增殖四甲基偶氮唑盐比色法检测EGF的体外功能。分别采用细胞凋亡实验、划痕实验和Transwell实验检测细胞的凋亡、侵袭和迁移。用MAPK激活试剂盒检测MAPK的磷酸化。EGF拮抗雷戈拉非尼对三种肝癌细胞株的生长抑制作用。经EGF处理后，Regorafenib对细胞生长的抑制作用可被阻断70%。EGF还阻断了Regorafenib诱导的细胞凋亡，以及Regorafenib诱导的细胞迁移和侵袭的减少。同时加入EGF受体拮抗剂Erlotinib可拮抗EGF的作用，表明EGF受体参与了EGF介导的阻断Regorafenib效应的机制。厄洛替尼还部分阻断了HPLS拮抗Regorafenib介导的生长抑制的作用，表明EGF是HPL作用的重要组成部分。所有这些结果表明，EGF拮抗Regorafenib介导的对肝癌细胞的生长和迁移抑制以及诱导细胞凋亡，并加强了微环境可以影响癌症药物作用的观点。
Blood platelet numbers are correlated to growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) also stimulated growth and migration, and antagonized the growth-inhibitory and apoptotic effects of both Sorafenib and Regorafenib, two multikinase inhibitors, on three HCC cell lines. In this study, in vitro function of human epidermal growth factor (EGF) with and without Sorafenib or Regorafenib was investigated. An ELISA kit was used to evaluate the EGF concentrations in hPLs. In vitro function of EGF was assessed with proliferation MTT test. Apoptosis assay, scratch assays, and Transwell assays were performed for apoptosis, invasion, and migration, respectively. MAPK Activation Kit was used to explore MAPK phosphorylation. EGF antagonized the growth inhibition of Regorafenib on three HCC cell lines. Regorafenib-mediated growth inhibition was blocked by 70 % when the cells were pre-treated with EGF. EGF also blocked Regorafenib-induced apoptosis, as well as Regorafenib-induced decreases in cell migration and invasion. The EGF effects were in turn antagonized by concomitant addition to the cultures of EGF receptor antagonist Erlotinib, showing that the EGF receptor was involved in the mechanisms of EGF-mediated blocking of Regorafenib effects. Erlotinib also partially blocked the effects of hPLs in antagonizing Regorafenib-mediated growth inhibition, showing that EGF was an important component of hPL actions. All these results show that EGF antagonized Regorafenib-mediated growth and migration inhibition and apoptosis induction in HCC cells and reinforce the idea that microenvironment can influence cancer drug actions.
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影响因子：
--
作者：
LEVIN, J;CONLEY, CL
通讯作者：
CONLEY, CL
影响因子：
3.5
作者：
Carr, Brian I.;Guerra, Vito;Pancoska, Petr
通讯作者：
Pancoska, Petr
影响因子：
13.5
作者：
Fuchs, Bryan C.;Hoshida, Yujin;Fujii, Tsutomu;Wei, Lan;Yamada, Suguru;Lauwers, Gregory Y.;McGinn, Christopher M.;DePeralta, Danielle K.;Chen, Xintong;Kuroda, Toshihiko;Lanuti, Michael;Schmitt, Anthony D.;Gupta, Supriya;Crenshaw, Andrew;Onofrio, Robert;Taylor, Bradley;Winckler, Wendy;Bardeesy, Nabeel;Caravan, Peter;Golub, Todd R.;Tanabe, Kenneth K.
通讯作者：
Tanabe, Kenneth K.
影响因子：
2.9
作者：
Schallmoser, Katharina;Bartmann, Christina;Strunk, Dirk
通讯作者：
Strunk, Dirk
GEP100/Arf6 是人肝癌 HepG2 细胞中表皮生长因子诱导的 ERK/Rac1 信号传导和细胞迁移所必需的
影响因子：
3.7
作者：
Hu Z;Du J;Yang L;Zhu Y;Yang Y;Zheng D;Someya A;Gu L;Lu X
通讯作者：
Lu X