Shen Xiaohui, Gu Yuejun, Yu Shengling, Gong Pihai, Mao Yuhang, Li Yiping, Zheng Ying, Qiao Fengchang, Zhao Zhujiang, Fan Hong
Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Department of Pathology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Exp Ther Med. 2019 May;17(5):4046-4054. doi: 10.3892/etm.2019.7459. Epub 2019 Apr 1.
Resistance to chemotherapeutic drugs leads to a poor prognosis in gastric cancer (GC). The present study aimed to assess the association between pituitary homeobox paired homeodomain transcription 1 (PITX1) expression and the sensitivity of GC cells to the chemotherapeutic drugs 5-fluorouracil (5-FU) and cisplatin (CDDP). In the present study, the gastric cancer cell lines GES-1, AGS, BGC-823, MCG-803 and SGC-7901 were used. The expression of PITX1 was determined via reverse transcription-quantitative polymerase chain reaction in GC cell lines. AGS and BGC-823 cells, which exhibit a decreased PITX1 expression, were transfected with a PITX1 cDNA construct and its control vector. MCG-803 and SGC-7901 cells, which exhibit an increased PITX1 expression, were transfected with siRNA against PITX1 and its control scramble sequence. A Cell Counting kit-8 assay was performed to determine the impact of PITX1 expression on the sensitivity of GC cells to 5-FU and CDDP. The Cancer Genome Atlas database was used to analyze the expression of PITX1 with GC prognosis in the Asian population and to assess the potential mechanism of PITX1 in 5-FU and CDDP resistance. The results revealed that the overexpression of PIXT1 increased the sensitivity of GC cells to 5-FU/CDDP. The combination of 5-FU/CDDP and PITX1 overexpression also reduced the proliferation of GC cells. Additionally, PIXT1 knockdown decreased the sensitivity of GC cells to 5-FU/CDDP. TCGA data revealed that a lower expression of PITX1 is exhibited in Asian GC patients than in normal individuals. GC patients with a lower expression of PITX1 had a poor prognosis. The expression of PITX1 affected the sensitivity of GC cells to 5-FU/CDDP, indicating that PITX1 may increase the efficacy of treatment in GC patients.
对化疗药物的耐药性导致胃癌（GC）预后不良。本研究旨在评估垂体同源框配对同源结构域转录因子1（PITX1）表达与GC细胞对化疗药物5-氟尿嘧啶（5-FU）和顺铂（CDDP）敏感性之间 的关联。在本研究中，使用了胃癌细胞系GES-1、AGS、BGC-823、MCG-803和SGC-7901。通过逆转录-定量聚合酶链反应测定GC细胞系中PITX1的表达。将PITX1表达降低的AGS和BGC-823细胞用PITX1 cDNA构建体及其对照载体转染。将PITX1表达增加的MCG-803和SGC-7901细胞用针对PITX1的小干扰RNA及其对照乱序序列转染。进行细胞计数试剂盒-8检测以确定PITX1表达对GC细胞对5-FU和CDDP敏感性的影响。利用癌症基因组图谱数据库分析亚洲人群中PITX1表达与GC预后的关系，并评估PITX1在5-FU和CDDP耐药中的潜在机制。结果显示，PITX1过表达增加了GC细胞对5-FU/CDDP的敏感性。5-FU/CDDP与PITX1过表达的联合使用也降低了GC细胞的增殖。此外，PITX1敲低降低了GC细胞对5-FU/CDDP的敏感性。癌症基因组图谱（TCGA）数据显示，亚洲GC患者中PITX1的表达低于正常个体。PITX1表达较低的GC患者预后较差。PITX1的表达影响了GC细胞对5-FU/CDDP的敏感性，表明PITX1可能提高GC患者的治疗效果。
