Apelin-13（F13A）对M2型肿瘤相关巨噬细胞诱导的乳腺癌细胞侵袭的影响及机制

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摘要目的探讨血管紧张素受体AT1相关的受体蛋白（APJ）拮抗剂Apelin13（F13A）对肿瘤相关巨噬细胞极化及其诱导的乳腺癌细胞系MCF-7细胞迁移和侵袭的影响。方法用白细胞介素-13（IL-13）（10 ng/mL）处理RAW264.7细胞24 h诱导M2型极化（M2RAW），同时用Apelin-13（F13A）（10.00 pm/mL）共同处理24 h，再与MCF-7细胞非接触共培养48 h。采用MTT法检测RAW和MCF-7细胞的增殖。采用酶联免疫吸附测定法检测RAW细胞培养液上清中TGF-β和IL-10水平。Western blot检测RAW细胞中M2型极化标志蛋白Arg-1表达。划痕实验和Transwell实验检测MCF-7细胞的迁移和侵袭力。结果与RAW组比较，M2RAW组TGF-β、IL-10及Arg-1的表达水平均显著增加，差异均有统计学意义（P < 0.05）；与M2RAW组比较，M2RAW+Apelin-13（F13A）组TGF-β、IL-10水平及Arg-1的表达水平显著降低，差异均有统计学意义（P < 0.05）。与RAW+MCF-7组比较，M2RAW+MCF-7组MCF-7细胞划痕显著减小，侵袭的细胞数明显增加，差异均有统计学意义（P < 0.05）；与M2RAW+MCF-7组比较，Apelin-13（F13A）+M2RAW+MCF-7组MCF-7细胞划痕显著增加，侵袭的细胞数明显减少，差异均有统计学意义（P < 0.05）。结论 Apelin13（F13A）可抑制巨噬细胞M2型极化及其诱导的乳腺癌细胞迁移和侵袭。

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	彭传真宋兆录李开艳吴晓冷宁

关键词 ：血管紧张素受体AT1相关的受体蛋白, 拮抗剂, 乳腺癌, 肿瘤侵袭, 肿瘤相关巨噬细胞, M2型极化

Abstract：Objective To investigate effect of putative receptor protein related to the angiotensin receptor AT1 (APJ) antagonist Apelin13 (F13A) on the polarization of tumor-associated macrophages (TAM) and the invasion induced by M2 type macrophages in breast cancer cells line MCF-7 cells. Methods Macrophage RAW264.7 cells were treated with IL-13 (10 ng/mL) for 24 h to induce M2 type polarization (M2RAW) and the cells were treated with Apelin-13(F13A) (10.00 pm/mL) for 24 h. RAW and MCF-7 cells were co-cultured for 48 h in non-contact manner. The proliferation of RAW and MCF-7 was detected by MTT. Levels of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) in culture medium were tested by ELISA. Expression of marker protein of M2 type polarization arginase 1 (Arg-1) were measured by Western blot. Migration and invasiveness of MCF-7 cells were tested by scratch test and Transwell method. Results Compared with RAW group, levels of TGF-β and IL-10 and expression of Arg-1 in M2RAW group were significantly increased, the differences were statistically significant (P < 0.05). Compared with M2RAW group, levels of TGF-β and IL-10 and expression of Arg-1 in M2RAW+Apelin-13 (F13A) group were significantly decreased, the differences were statistically significant (P < 0.05). Compared with RAW+MCF-7 group, scratch area was significantly decreased, the number of cell through the membrane was significantly increased in M2RAW+MCF-7 group, the differences were statistically significant (P < 0.05). Compared with M2RAW+MCF-7 group, scratch area was significantly increased, the number of cell through the membrane was significantly decreased in Apelin-13(F13A)+M2RAW+MCF-7 group, the differences were statistically significant (P < 0.05). Conclusion Apelin13 (F13A) inhibits the polarization of tumor related macrophages and the invasion induced by M2 type macrophages in breast cancer cells line MCF-7 cells.

Key words： Putative receptor protein related to the angiotensin receptor AT1 Antagonists Mammary cancer Tumor invasion Tumor-associated macrophages M2 type polarization

通讯作者: 宋兆录（1976.3-），男，硕士，副主任医师；研究方向：乳腺癌的防治。

作者简介: 彭传真（1980.9-），女，硕士；研究方向：乳腺癌的防治。

引用本文:

彭传真宋兆录李开艳吴晓冷宁. Apelin-13（F13A）对M2型肿瘤相关巨噬细胞诱导的乳腺癌细胞侵袭的影响及机制[J]. 中国医药导报, 2018, 15(15): 13-17,42.
PENG Chuanzhen SONG Zhaolu LI Kaiyan WU Xiao LENG Ning. Effect of putative receptor protein related to the angiotensin receptor AT1 antagonist Apelin13 (F13A) on the invasion induced by M2 type tumor related macrophages in breast cancer cells line MCF-7 cells and probable mechanism. 中国医药导报, 2018, 15(15): 13-17,42.

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