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维甲酸脂肪酰胺抑制人卵巢癌中的AMPK-HIF-1α通路。

Retinoic acid aliphatic amide inhibits the AMPK-HIF-1α pathway in human ovarian cancer.

作者信息

Yu Xiao-Lan, Xia Ji-Yi, Ye Hai-Qiong, Li Xia, Zhang Yu-Jiao, Mao Xi-Guang

机构信息

Department of Obstetrics and Gynecology, The Affiliated TCM Hospital of Sichuan Medical University Sichuan, 646000, China.

Researh Center for Drug and Functional Food of Sichuan Medical University Sichuan, 646000, China.

出版信息

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6416-24. eCollection 2015.

Abstract

Ovarian carcinoma the commonly observed gynecological cancers has a high mortality rate. In the present study effect of retinoic acid aliphatic amide (RACA) in ovarian cancer cells was investigated using proliferation, migration and invasion assays. Western blot was used to examine the Bcl-2, cleaved caspase 3, p-ERK, MMP-2, p-FAK, P-P38, p-AMPKα and HIF-1α protein expression. CoCl2 was used to induce HIF-1α expression in SKOV3ip. 1 and HEY-A8 cells. The results revealed that RACA treatment prompted cell proliferation, invasion and migration but inhibited apoptosis of SKOV3ip. 1 and HEY-A8 cells. RACA treatment also induced upregulation of Bcl-2 and MMP-2, activation of p-P38, p-ERK and p-FAK, inhibition of cleaved caspase 3. RACA treatment also caused upregulatation of HIF-1α in ovarian cells with the activation of p-AMPKα. Upregulation of HIF-1α expression in CoCl2-treated cancer cells resulted in decrease in SDHB. Thus RACA plays a key role in cell proliferation, invasion, migration and apoptosis of human ovarian carcinoma through AMPK-HIF-1α pathway.

摘要

卵巢癌是常见的妇科癌症,死亡率很高。在本研究中,使用增殖、迁移和侵袭试验研究了维甲酸脂肪酰胺(RACA)对卵巢癌细胞的作用。采用蛋白质印迹法检测Bcl-2、裂解的半胱天冬酶3、磷酸化细胞外调节蛋白激酶(p-ERK)、基质金属蛋白酶2(MMP-2)、磷酸化粘着斑激酶(p-FAK)、磷酸化p38(P-P38)、磷酸化腺苷酸活化蛋白激酶α(p-AMPKα)和缺氧诱导因子-1α(HIF-1α)蛋白表达。使用氯化钴(CoCl2)诱导SKOV3ip.1和HEY-A8细胞中HIF-1α的表达。结果显示,RACA处理促进了SKOV3ip.1和HEY-A8细胞的增殖、侵袭和迁移,但抑制了其凋亡。RACA处理还诱导了Bcl-2和MMP-2的上调、p-P38、p-ERK和p-FAK的激活、裂解的半胱天冬酶3的抑制。RACA处理还导致卵巢细胞中HIF-1α的上调以及p-AMPKα的激活。CoCl2处理的癌细胞中HIF-1α表达的上调导致琥珀酸脱氢酶亚基B(SDHB)减少。因此,RACA通过AMPK-HIF-1α途径在人卵巢癌的细胞增殖、侵袭、迁移和凋亡中起关键作用。

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