Open AccessGlutathione S‐transferase Pi 1 is a valuable predictor for cancer drug resistance in esophageal squamous cell carcinoma
Author(s) -
Ogino Shinpei,
Konishi Hirotaka,
Ichikawa Daisuke,
Matsubara Daiki,
Shoda Katsutoshi,
Arita Tomohiro,
Kosuga Toshiyuki,
Komatsu Shuhei,
Shiozaki Atsushi,
Okamoto Kazuma,
Kishimoto Mitsuo,
Otsuji Eigo
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13896
Subject(s) - cisplatin , apoptosis , gene knockdown , cancer research , malignancy , cell growth , medicine , drug resistance , cancer , chemotherapy , glutathione , biology , pathology , oncology , enzyme , biochemistry , genetics , microbiology and biotechnology
Esophageal squamous cell carcinoma ( ESCC ) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S‐transferase Pi 1 ( GSTP 1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP 1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP 1 expression were examined in ESCC cell lines. Proliferation of GSTP 1 knockdown cells was significantly decreased ( P < .01), and the frequency of early apoptosis was increased ( P < .05). Invasion capacity of GSTP 1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP 1 plays an important role in malignant potential. To examine the effects of GSTP 1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP 1 knockdown cells treated with cisplatin was lower than that of control cells ( P < .01). Moreover, the frequency of early and late apoptosis in GSTP 1 knockdown cells was markedly increased over that of control cells by cisplatin exposure ( P < .01). In immunohistochemistry assay of resected tissue samples, GSTP 1 expression was significantly associated with clinical downstaging ( P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP 1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy ( P = .02). In summary, GSTP 1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.