Preclinical Evaluation of Exemestane as a Novel Chemotherapy for Gastric Cancer

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Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/112907

Title:	Preclinical Evaluation of Exemestane as a Novel Chemotherapy for Gastric Cancer
Authors:	楊顓丞;張寧;吳登強;鄭維中;鍾瑋敏;張維君;Liu, C-J;Liu, C-J;吳宜珍;賴學洲;馬文隆;Ma, Wen-Lung
Contributors:	護理學系
Keywords:	aromatase;exemestane;gastric cancer.
Date:	2019-11
Issue Date:	2020-09-02 08:00:48 (UTC+0)
Publisher:	亞洲大學
Abstract:	CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single-cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian-based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5-Fluorouracil (5-FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar-targeting compounds were tested, and the results showed that exemestane exhibited superior cancer-suppressing efficacy to other ARIs. In addition, exemestane down-regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5-FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose-dependent manner. Combining subminimal doses of 5-FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5-FU and exemestane for GCa therapy is recommended.
Relation:	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Appears in Collections:	[Department of Nursing] Journal Article

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