level 2
rlbell
楼主
针对病种：肺癌
发表时间：2012年4月
发表国家：荷兰
登载刊物：分子生物学报告
研究单位：中国广州南方医科大学公共卫生学院和热带医学院儿童和青少年健康系等
研究人员：朱航、 程华、 任远等
主要结论：染料木黄酮增强了吉非替尼对携带 T790M 突变非小细胞肺癌的抗肿瘤作用。这种协同作用可能是因为抑制下游分子和 EGFR 促凋亡作用的增强。
Molecular Biology Reports, 2012, 39(4):4971-4979.
Synergistic inhibitory effects by the combination of gefitinib and genistein on NSCLC with acquired drug-resistance in vitro and in vivo
Hang Zhu, Hua Cheng, Yuan Ren, et al
Department of Child and Adolescent Health, School of Public Health and Tropical Medicine Southern Medical University Guangzhou, China; et al
In clinical practice, most patients with non small cell lung cancer (NSCLC) who respond to tyrosine kinase inhibitors eventually progress because of an acquired resistance mutation, T790M, in epidermal growth factor receptor (EGFR). Thus, it is important to identify a new drug to reduce resistance. The aim of this study was to test whether genistein combined with gefitinib is effective against NSCLC in a cell line carrying T790M, and to clarify the underlying mechanisms. The human lung cancer cell line H1975 was used as an in vitro and in vivo model. Cells were treated with gefitinib, genistein, or a combination at a range of concentrations. Cell proliferation was calculated to assess the anticancer effects of the compounds in vitro. Flow cytometry and Western blotting were employed to determine the inhibitory effects on proliferation and the induction of apoptosis. The in vivo effects of the compounds were examined using a xenografted nude mouse model for validation. Gefitinib together with genistein enhanced both growth inhibition and apoptosis; however, the greatest synergistic effect was observed at low concentrations. p-EGFR, p-Akt, and p-mTOR expressions in vitro were reduced more by the combined use of the drugs, whereas caspase-3 and PARP activities were increased. Significantly more tumor growth inhibition was detected following combination treatment in the in vivo model. These findings suggest that genistein enhanced the antitumor effects of gefitinib in a NSCLC cell line carrying the T790M mutation. This synergistic activity may be due to increased inhibition of the downstream molecular and pro-apoptotic effects of EGFR.
2020年04月07日 07点04分
1
发表时间：2012年4月
发表国家：荷兰
登载刊物：分子生物学报告
研究单位：中国广州南方医科大学公共卫生学院和热带医学院儿童和青少年健康系等
研究人员：朱航、 程华、 任远等
主要结论：染料木黄酮增强了吉非替尼对携带 T790M 突变非小细胞肺癌的抗肿瘤作用。这种协同作用可能是因为抑制下游分子和 EGFR 促凋亡作用的增强。
Molecular Biology Reports, 2012, 39(4):4971-4979.
Synergistic inhibitory effects by the combination of gefitinib and genistein on NSCLC with acquired drug-resistance in vitro and in vivo
Hang Zhu, Hua Cheng, Yuan Ren, et al
Department of Child and Adolescent Health, School of Public Health and Tropical Medicine Southern Medical University Guangzhou, China; et al
In clinical practice, most patients with non small cell lung cancer (NSCLC) who respond to tyrosine kinase inhibitors eventually progress because of an acquired resistance mutation, T790M, in epidermal growth factor receptor (EGFR). Thus, it is important to identify a new drug to reduce resistance. The aim of this study was to test whether genistein combined with gefitinib is effective against NSCLC in a cell line carrying T790M, and to clarify the underlying mechanisms. The human lung cancer cell line H1975 was used as an in vitro and in vivo model. Cells were treated with gefitinib, genistein, or a combination at a range of concentrations. Cell proliferation was calculated to assess the anticancer effects of the compounds in vitro. Flow cytometry and Western blotting were employed to determine the inhibitory effects on proliferation and the induction of apoptosis. The in vivo effects of the compounds were examined using a xenografted nude mouse model for validation. Gefitinib together with genistein enhanced both growth inhibition and apoptosis; however, the greatest synergistic effect was observed at low concentrations. p-EGFR, p-Akt, and p-mTOR expressions in vitro were reduced more by the combined use of the drugs, whereas caspase-3 and PARP activities were increased. Significantly more tumor growth inhibition was detected following combination treatment in the in vivo model. These findings suggest that genistein enhanced the antitumor effects of gefitinib in a NSCLC cell line carrying the T790M mutation. This synergistic activity may be due to increased inhibition of the downstream molecular and pro-apoptotic effects of EGFR.