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细胞周期调控与胃癌细胞对 5-氟尿嘧啶的耐药性有关。

Cell Cycle Dysregulation Is Associated With 5-Fluorouracil Resistance in Gastric Cancer Cells.

机构信息

Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

出版信息

Anticancer Res. 2020 Jun;40(6):3247-3254. doi: 10.21873/anticanres.14306.

Abstract

BACKGROUND/AIM: 5-Fluorouracil (5-FU) is an anticancer drug commonly used to treat gastric cancer; however, continuous 5-FU chemotherapy causes drug resistance.

MATERIALS AND METHODS

We established five sublines of 5-FU-resistant AGS gastric cancer cells to investigate changes that may have occurred in the development of 5-FU resistance. Drug resistance to other chemotherapeutic reagents, proliferation, cell-cycle changes, and wound healing ability were assessed for each subline.

RESULTS

Retarded cell growth, G/G phase arrest, up-regulation of p57, and down-regulation of cyclin D1 were commonly observed in all five sublines. Resistance to paclitaxel and cisplatin was also observed in most of the sublines.

CONCLUSION

Our data support the notion that G/G arrest due to changes in p57 and cyclin D1 expression may confer drug resistance, while EMT seems non-essential to 5-FU resistance in AGS gastric carcinoma cells.

摘要

背景/目的:5-氟尿嘧啶(5-FU)是一种常用于治疗胃癌的抗癌药物;然而,连续使用 5-FU 化疗会导致药物耐药性。

材料和方法

我们建立了五种耐 5-FU 的 AGS 胃癌细胞亚系,以研究在 5-FU 耐药性发展过程中可能发生的变化。评估了每个亚系对其他化疗试剂的耐药性、增殖、细胞周期变化和伤口愈合能力。

结果

所有五种亚系均表现出细胞生长缓慢、G1/G0 期阻滞、p57 上调和 cyclin D1 下调。大多数亚系也表现出对紫杉醇和顺铂的耐药性。

结论

我们的数据支持这样一种观点,即 p57 和 cyclin D1 表达的变化导致的 G1/G0 期阻滞可能赋予药物耐药性,而 EMT 对于 AGS 胃癌细胞中 5-FU 耐药性似乎并非必需。

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