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Retinoic acid aliphatic amide inhibits the AMPK-HIF-1α pathway in human ovarian cancer
Authors:Xiao-Lan Yu  Ji-Yi Xia  Hai-Qiong Ye  Xia Li  Yu-Jiao Zhang  Xi-Guang Mao
Institution:1.Department of Obstetrics and Gynecology, The Affiliated TCM Hospital of Sichuan Medical University, Sichuan, 646000, China;2.Researh Center for Drug and Functional Food of Sichuan Medical University, Sichuan, 646000, China;3.Department of Obstetrics and Gynecology, Affiliated Hospital of Sichuan Medical University, Sichuan, 646000, China;4.Department of Obstetrics and Gynecology, The Hosipital of Traditional Chinese Medicine of Leshan, Sichuan, 614000, China
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.
Keywords:Tumor progression  HIF-1α    AMPK  gene silence  ovarian carcinoma  apoptosis
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