Glutathione S‐transferase Pi 1 is a valuable predictor for cancer drug resistance in esophageal squamous cell carcinoma

Summary

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S‐transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. The proliferation of GSTP1 knockdown cells was significantly decreased (p<0.01), and the frequency of early apoptosis was increased (p<0.05). The invasion capacity of GSTP1 knockdown cells was slightly decreased in trans‐well assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug‐resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were performed. The viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (p<0.01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells　was markedly increased than that of control cells by cisplatin exposure (p<0.01). In immunohistochemistry assay of the resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (p=0.04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there is a significant association between the GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (p=0.02). In summary, GSTP1 was related to the malignant potential and may be a predictive marker of drug resistance in ESCC patients.

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