Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China; Department of Health Management, Chongqing Bishan District People's Hospital, Chongqing, 402760, China.
Department of E.N.T, Chongqing Bishan District People's Hospital, Chongqing, 402760, China.
Biochem Biophys Res Commun. 2020 Oct 20;531(3):364-371. doi: 10.1016/j.bbrc.2020.07.049. Epub 2020 Aug 14.
Breast cancer is a malignant disease and a great cause of morbidity and mortality in women. The etiology of breast cancer is complex and closely related to people's living habits. Lapatinib, a tyrosine-kinase inhibitor, blocks the activation of the HER1 and HER2 tyrosine kinase to inhibit the activation of downstream signaling pathways and thus inhibit tumor survival and proliferation. This study aimed to explore to the combination of lapatinib and luteolin on human breast cancer. The combination of lapatinib and luteolin increased the sensitivity of SKBR-3, BT-474 and ZR-75-1 cells. This combination equally up-regulated the expression of FOXO3a and NQO1 and their downstream target genes Bim, GADD45, P21, and the phosphorylation level of FOXO3a protein decreased. The mice transplanted with BT-474 cells, the volume of subcutaneous tumors in the luteolin group, lapatinib group, and lapatinib + luteolin group were significantly smaller than the control group. The results of Western blot showed that in tumor tissues of mice transplanted with BT-474 cells, the expression levels of FOXO3a and NQO1 protein in the luteolin group, lapatinib group, and lapatinib + luteolin group were all obviously upregulated, the mice transplanted with ZR-75-1 cells exhibited similar results. These data suggest that the combination of lapatinib and luteolin may inhibit HER2 human breast cancer by significantly increasing the expression of FOXO3a and NQO1, two key genes in HER2 human breast cancer xenografts.
乳腺癌是一种恶性疾病，也是导致女性发病率和死亡率高的主要原因之一。乳腺癌的病因复杂，与人们的生活习惯密切相关。拉帕替尼是一种酪氨酸激酶抑制剂，可阻断 HER1 和 HER2 酪氨酸激酶的激活，抑制下游信号通路的激活，从而抑制肿瘤的存活和增殖。本研究旨在探讨拉帕替尼与木犀草素联合应用于人乳腺癌。拉帕替尼与木犀草素联合应用增加了 SKBR-3、BT-474 和 ZR-75-1 细胞的敏感性。这种联合用药同样上调了 FOXO3a 和 NQO1 的表达及其下游靶基因 Bim、GADD45、P21 的表达，同时降低了 FOXO3a 蛋白的磷酸化水平。BT-474 细胞移植的小鼠中，木犀草素组、拉帕替尼组和拉帕替尼+木犀草素组的皮下肿瘤体积明显小于对照组。Western blot 结果显示，在 BT-474 细胞移植的小鼠肿瘤组织中，木犀草素组、拉帕替尼组和拉帕替尼+木犀草素组的 FOXO3a 和 NQO1 蛋白表达水平均明显上调，移植 ZR-75-1 细胞的小鼠也表现出类似的结果。这些数据表明，拉帕替尼与木犀草素联合应用可能通过显著增加 HER2 人乳腺癌异种移植中两个关键基因 FOXO3a 和 NQO1 的表达来抑制 HER2 人乳腺癌。
