Ju Jing, Wang Nan, Wang Jiali, Wu Fanrong, Ge Jinfang, Chen Feihu
School of Pharmacy, Anhui Medical University, Hefei, People's Republic of China.
Department of Pharmacy, Anqing Municipal Hospital, Anqing Anhui, People's Republic of China.
Drug Des Devel Ther. 2018 Apr 27;12:997-1008. doi: 10.2147/DDDT.S151029. eCollection 2018.
4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel retinoid derivative, inhibits proliferation and induces differentiation in many cancer cells. In this study, the inhibitory effects of ATPR on the proliferation, invasion, and migration of breast cancer (BC) cells, and the relationship between ATPR and the expression of the intracellular lipid-binding proteins CRABP2 and FABP5 were investigated.
CRABP2 and FABP5 expression was evaluated in infiltrating breast-infiltrating ductal carcinoma(BIDC) and benign breast fibroma (BBF) by immunohistochemistry and in MCF-7, MDA-MB-231, MDA-MB-435, and MDA-MB-453 cells by immunofluorescence. The inhibition of proliferation by ATPR in these cells was detected by MTT. After downregulation and upregulation of CRABP2 and FABP5 in MCF-7 or MDA-MB-231 cells using siRNA and plasmids, the effect of ATPR on proliferation was detected by MTT and real-time cell analysis, and the effects of ATPR on the invasion and migration of MDA-MB-231 cells were detected using a Boyden chamber assay and a wound healing assay.
CRABP2 expression was moderately or strongly positive in BIDC and BBF. FABP5 expression was also moderately or strongly positive in BIDC, but weakly positive or negative in BBF. CRABP2 and FABP5 were highly expressed in MCF-7 cells, moderately expressed in MDA-MB-453 cells, and weakly expressed in MDA-MB-435 and MDA-MB-231 cells. ATPR inhibited proliferation more strongly in MCF-7 cells than in other cells. The inhibition of proliferation by ATPR depended on an increase in CRABP2, but not FABP5 expression. A decrease in FABP5 could inhibit the invasion and migration of BC cells.
These findings indicate that ATPR might inhibit proliferation by upregulating CRABP2, and inhibit invasion and migration by downregulating FABP5 in BC cells. These findings may facilitate the use of differentiation therapy in BC.
4-氨基-2-三氟甲基苯基维甲酸酯（ATPR）是一种新型维甲酸衍生物，可抑制多种癌细胞的增殖并诱导其分化。本研究调查了ATPR对乳腺癌（BC）细胞增殖、侵袭和迁移的抑制作用，以及ATPR与细胞内脂质结合蛋白CRABP2和FABP5表达之间的关系。
采用免疫组织化学法评估浸润性乳腺浸润性导管癌（BIDC）和乳腺良性纤维瘤（BBF）中CRABP2和FABP5的表达，采用免疫荧光法评估MCF-7、MDA-MB-231、MDA-MB-435和MDA-MB-453细胞中CRABP2和FABP5的表达。通过MTT法检测ATPR对这些细胞增殖的抑制作用。使用小干扰RNA（siRNA）和质粒下调和上调MCF-7或MDA-MB-231细胞中CRABP2和FABP5的表达后，通过MTT法和实时细胞分析检测ATPR对增殖的影响，并使用Boyden小室试验和伤口愈合试验检测ATPR对MDA-MB-231细胞侵袭和迁移的影响。
CRABP2在BIDC和BBF中呈中度或强阳性表达。FABP5在BIDC中也呈中度或强阳性表达，但在BBF中呈弱阳性或阴性表达。CRABP2和FABP5在MCF-7细胞中高表达，在MDA-MB-453细胞中中度表达，在MDA-MB-435和MDA-MB-231细胞中低表达。ATPR对MCF-7细胞增殖的抑制作用强于其他细胞。ATPR对增殖的抑制作用取决于CRABP2表达的增加，而不是FABP5表达的增加。FABP5的降低可抑制BC细胞的侵袭和迁移。
这些发现表明，ATPR可能通过上调CRABP2抑制增殖，并通过下调FABP5抑制BC细胞的侵袭和迁移。这些发现可能有助于BC的分化治疗。
