Li Wei, Liu Xu, Zhang Guoqian, Zhang Linlin
Department of Laboratory, First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Department of Oncology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Zhongguo Fei Ai Za Zhi. 2017 Aug 20;20(8):555-561. doi: 10.3779/j.issn.1009-3419.2017.08.10.
It has been proven that chlorogenic acids can produce anticancer effects by regulating cell cycle, inducing apoptosis, inhibiting cell growth, Notch signaling pathways are closely related to many human tumors. The aim of this study is to study the mechanism of chlorogenic acid on apoptosis of non-small lung cancer through Notch1 pathway in animal level, and hope to provide theory basis on clinical treatment and research aimed at targeting Notch1 signaling in non-small cell carcinoma (NSCLC).
MTT assay was used to evaluate the A549 cell proliferation under the treatment of chlorogenic acid. The effect of chlorogenic acid on apoptotic and cell cycle were detected by flow cytometry. The animal model of A549 cell transplanted in nude was established, tumer size and weight were detected. The mRNA level of Notch1 signal pathway related facter were detected by RT-PCR; the expression of Notch1 signal pathway related facter in tumor tissue was detected by western blot.
Chlorogenic acid inhibited the A549 cell proliferation. incresed cell apoptotic and cell percentagein G2/M (P<0.05), and in a dose-dependent manner. In animal model, tumer size and weight were lower than control group, the difference was statistically significant (P<0.05). The relative expression of mRNA of Notch1, VEGF, Delta4, HES1 and HEY1 were decreaced (P<0.05) in tumor tissue which treated with chlorogenic. The expression of Notch1 were decreaced, PTEN, p-PTEN, p-AKT were increced significantly in tumor tissue which treated with chlorogenic (P<0.05).
Chlorogenic acid can regulate theapoptosis of non-small lung cancer through Notch pathway in animal level, which may be associated with the down-regulating the expression of VEGF and Delta4. Notch pathway may cross talk with PI3K/AKT pathway through PTEN in NSCLC.
已证实绿原酸可通过调节细胞周期、诱导凋亡、抑制细胞生长发挥抗癌作用，Notch信号通路与多种人类肿瘤密切相关。本研究旨在从动物水平研究绿原酸通过Notch1通路对非小细胞肺癌凋亡的作用机制，希望为针对非小细胞肺癌Notch1信号的临床治疗和研究提供理论依据。
采用MTT法评估绿原酸处理下A549细胞的增殖情况。通过流式细胞术检测绿原酸对细胞凋亡和细胞周期的影响。建立A549细胞裸鼠移植瘤模型，检测肿瘤大小和重量。采用RT-PCR检测Notch1信号通路相关因子的mRNA水平；采用蛋白质免疫印迹法检测肿瘤组织中Notch1信号通路相关因子的表达。
绿原酸抑制A549细胞增殖，增加细胞凋亡率及G2/M期细胞百分比（P<0.05），且呈剂量依赖性。在动物模型中，肿瘤大小和重量均低于对照组，差异有统计学意义（P<0.05）。绿原酸处理的肿瘤组织中，Notch1、VEGF、Delta4、HES1和HEY1的mRNA相对表达量降低（P<0.05）。绿原酸处理的肿瘤组织中，Notch1表达降低，PTEN、p-PTEN、p-AKT表达显著增加（P<0.05）。
绿原酸在动物水平可通过Notch通路调节非小细胞肺癌细胞凋亡，可能与下调VEGF和Delta4表达有关。在非小细胞肺癌中，Notch通路可能通过PTEN与PI3K/AKT通路相互作用。
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