Department of Oncology Center, First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510407, Guangdong, China.
South China University of Technology School of Medicine, Guangzhou 520006, Guangdong, China.
Cancer Biomark. 2018;21(4):787-795. doi: 10.3233/CBM-170483.
Aplysia ras homology member I/ARHI is known as ovarian cancer suppressor gene and potential inhibitor of signal transducer and activator of transcription 3/STAT3 signaling. Resveratrol suppresses growth and STAT3 activation of ovarian cancer cells, while its influence in ARHI expression remains unknown.
The current study aims to elucidate the status of ARHI expression and its relevance with growth suppression and STAT3 inactivation of resveratrol-treated cells.
ARHI expression patterns of three ovarian cancer cell lines (human CAOV-3, OVCAR-3 and rat NUTU-19) without and with 100 μM resveratrol treatment were checked by immunocytochemical staining, Western blotting and RT-PCR. The involvement of ARHI in the growth inhibition and STAT3 inactivation of resveratrol-treated OVCAR-3 cells was investigated by transfection of ARHI-specific siRNA.
ARHI is expressed in low levels in three ovarian cancer cell lines, which is upregulated upon resveratrol treatment accompanied with growth arrest, extensive apoptosis, increased autophagic activity and inactivated STAT3 signaling. Specific siRNA transfection efficiently knocked down ARHI expression in resveratrol-treated CAOV-3 and OVCAR-3 cells and increased the total cell number in limited extents (P> 0.05) in comparison with that of resveratrol-treated ovarian cancer cells without any transfection or transfected with mock oligonucleotides. ARHI knockdown failed to prevent resveratrol-caused STAT3 inactivation and cell crisis.
ARHI upregulation is another molecular event caused by resveratrol and one of the elements related with resveratrol's anti-ovarian cancer efficacy. Resveratrol may inactivate STAT3 signaling of ovarian cancer cells in ARHI unrelated pattern(s).
Aplysia ras 同源物 I/ARHI 被认为是卵巢癌抑制基因和信号转导子和转录激活因子 3/STAT3 信号的潜在抑制剂。白藜芦醇抑制卵巢癌细胞的生长和 STAT3 激活，但其对 ARHI 表达的影响尚不清楚。
本研究旨在阐明 ARHI 表达的状况及其与白藜芦醇处理细胞生长抑制和 STAT3 失活的相关性。
通过免疫细胞化学染色、Western blot 和 RT-PCR 检查三种卵巢癌细胞系（人 CAOV-3、OVCAR-3 和大鼠 NUTU-19）在没有和有 100μM 白藜芦醇处理时的 ARHI 表达模式。通过转染 ARHI 特异性 siRNA 研究 ARHI 在白藜芦醇处理的 OVCAR-3 细胞生长抑制和 STAT3 失活中的作用。
ARHI 在三种卵巢癌细胞系中低表达，白藜芦醇处理后表达上调，伴随生长停滞、广泛凋亡、自噬活性增加和 STAT3 信号失活。特异性 siRNA 转染可有效敲低白藜芦醇处理的 CAOV-3 和 OVCAR-3 细胞中的 ARHI 表达，但与未转染或转染 mock 寡核苷酸的白藜芦醇处理卵巢癌细胞相比，总细胞数仅略有增加（P>0.05）。ARHI 敲低未能阻止白藜芦醇引起的 STAT3 失活和细胞危机。
ARHI 的上调是白藜芦醇引起的另一个分子事件，也是白藜芦醇抗卵巢癌疗效相关的因素之一。白藜芦醇可能以 ARHI 不相关的模式（s）使卵巢癌细胞的 STAT3 信号失活。
