黄卡瓦胡椒素B抑制HER2阳性乳腺癌细胞增殖的作用机制  

Mechanism of Flavokawain B inhibiting the proliferation of HER2 positive breast cancer cells

作　　者：唐颖 李雪森 TANG Ying;LI Xue-sen(Institute for Cancer Medicine and School of Basic Medical Sciences,Southwest Medical University,Luzhou 646000,Sichuan,China)

机构地区：[1]西南医科大学基础医学院肿瘤医学研究所,泸州646000

出　　处：《医学研究生学报》2022年第9期919-924,共6页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81603154)。

摘　　要：目的 黄卡瓦胡椒素B(FKB)已在多种肿瘤中显示出抗癌活性,但在人表皮生长因子受体2(HER2)阳性乳腺癌中研究尚少。文中旨在探讨FKB抑制HER2阳性的乳腺癌细胞增殖的机制。方法 培养乳腺癌HER2阳性细胞株BT474、MDA-MB-453、SKBR3,以及HER2阴性细胞株T47D、MCF-7、MDA-MB-231、MDA-MB-468、ZR-75-30、SUM159。不同浓度的FKB处理细胞48 h后,采用CCK-8法检测FKB对BT474、MDA-MB-453、SKBR3细胞增殖的影响。Western blot法检测40μmol/L FKB处理16 h后对不同乳腺癌细胞HER2-AKT信号通路相关蛋白表达。采用q-PCR技术检测FKB对BT474、MDA-MB-453的HER2的mRNA水平的影响。结果 FKB能抑制BT474、MDA-MB-453、SKBR3细胞的增殖,且抑制作用呈浓度依赖性。Western blot结果显示,使用FKB处理16h后,3种HER2阳性乳腺癌细胞的HER2蛋白和p-AKT蛋白的表达水平明显降低(P<0.05)。FKB能抑制由EGF诱导的AKT磷酸化的上调。q-PCR结果显示,FKB作用16h后,BT474、MDA-MB-453的HER2的mRNA水平明显降低(P<0.05)。与EGF(193±3)比较,FKB+EGF(60±13)与K2206+FKB(108±21)均能抑制EGF诱导的细胞增殖水平(P<0.05)。结论 FKB通过HER2-AKT通路抑制HER2阳性乳腺癌细胞的增殖,为临床靶向HER2治疗乳腺癌提供新的策略。Objective Flavokawain B has shown anticancer activity in a variety of tumors, but has been little studied in HER2-positive breast cancer. This study investigated the mechanism that Flavokawain B inhibits the proliferation of HER2-positive breast cancer cells. Methods HER2-positive cell lines BT474, MDA-MB-453, SKBR3, and HER2-negative cell lines T47 D, MCF-7, MDA-MB-231, MDA-MB-468, ZR-75-30, SUM159 were cultured. After cells were treated with different concentrations of Flavokawain B for 48 h. CCK-8 method was used to detect the effects of Flavokawain B on the proliferation of BT474, MDA-MB-453 and SKBR3 cells. Western blotting was used to detect the expression of HER2-AKT signaling pathway related proteins in different breast cancer cells treated with 40 μmol/L Flavokawain B for 16 h. Q-PCR was used to detect the effect of Flavokawain B on HER2 mRNA levels of BT474 and MDA-MB-453. Results In vitro, the proliferation of BT474, MDA-MB-453 and SKBR3 cells were inhibited in a concentration-dependent manner. Further studies showed that the proliferation of BT474 cells induced by EGF was inhibited by Flavokawain B. Western blotting results showed that the expression levels of HER2 protein and p-AKT protein were significantly decreased in 3 HER2-positive breast cancer cells after 16 h treatment(P<0.05), while the expression levels of p-AKT protein were not decreased in HER2-negative breast cancer cells. In addition, Flavokawain B inhibited EGF-induced up-regulation of AKT phosphorylation. Q-PCR results showed that the mRNA levels of HER2 in BT474 and MDA-MB-453 were significantly decreased after treatment for 16 hours(P<0.05). Conclusion FKB inhibits the proliferation of HER2-positive breast cells through the HER2-AKT pathway, which provides a new strategy for the clinical treatment of breast cancer targeting HER2.

关 键 词：乳腺癌 黄卡瓦胡椒素B HER2-AKT信号通路 

分 类 号：R737.9[医药卫生—肿瘤]