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谷胱甘肽 S-转移酶 Pi 1 是预测食管鳞癌癌症药物耐药性的有价值标志物。

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

机构信息

Division of Digestive surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

出版信息

Cancer Sci. 2019 Feb;110(2):795-804. doi: 10.1111/cas.13896. Epub 2018 Dec 21.

Abstract

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. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell 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 carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.

摘要

食管鳞状细胞癌(ESCC)是一种致命的恶性肿瘤。然而,目前用于诊断和治疗的有效标志物很少。谷胱甘肽 S-转移酶 Pi 1(GSTP1)已被报道可作为某些癌症恶性程度或抗癌药物耐药性的预测指标。我们研究了 GSTP1 表达与 ESCC 细胞系和临床组织样本中的恶性程度或药物耐药性的关系。我们在 ESCC 细胞系中检测了 GSTP1 表达与增殖和凋亡的关系。GSTP1 敲低细胞的增殖明显降低(P<.01),早期凋亡频率增加(P<.05)。在 Transwell 实验中,GSTP1 敲低细胞的侵袭能力略有下降。这些结果表明 GSTP1 在恶性潜能中发挥重要作用。为了研究 GSTP1 对耐药性的影响,我们进行了顺铂暴露下的化疗敏感性测定和凋亡测定。用顺铂处理的 GSTP1 敲低细胞的活力低于对照细胞(P<.01)。此外,与对照细胞相比,GSTP1 敲低细胞经顺铂处理后早期和晚期凋亡的频率明显增加(P<.01)。在 72 例接受新辅助化疗的 ESCC 患者的切除组织样本免疫组化检测中,GSTP1 表达与临床降期显著相关(P=.04)。此外,在 34 例未接受新辅助化疗的 ESCC 患者的切除组织和活检样本中,GSTP1 表达也存在显著相关性(P=.02)。总之,GSTP1 与恶性潜能相关,可能是 ESCC 患者药物耐药性的预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc51/6361570/89ddbec1777d/CAS-110-795-g001.jpg

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