Suppression of ID1 expression in colon cancer cells increases sensitivity to 5-fluorouracil
Suppression of ID1 expression in colon cancer cells increases sensitivity to 5-fluorouracil
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DOI：
10.18388/abp.2016_1421
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发表时间：
2017-01-01
影响因子：
1.7
通讯作者：
Pawelczyk, Tadeusz
中科院分区：
文献类型：
--
作者：
Przybyla, Tomasz;Sakowicz-Burkiewicz, Monika;Pawelczyk, Tadeusz
5-氟尿嘧啶辅助化疗仍是晚期结直肠癌的基本治疗方法。成功治疗的主要障碍是CRC细胞获得化学抗性的能力。在这里，我们研究了ID1沉默对CRC细胞对5-FU敏感性的影响。为了抑制HT-29和HCT-116细胞中的ID1表达，用携带ID1沉默序列的慢病毒载体转导细胞。与亲本细胞相比，ID1沉默的细胞显示上皮和间充质标志物的表达改变，并表现出增加的增殖率。抑制ID1的HCT-116细胞对5-FU变得敏感，而HT-29细胞中未观察到这一点。沉默ID1导致编码代谢5-FU的酶的基因表达改变。抑制ID1的HT-29细胞胸苷磷酸化酶、尿苷-胞苷激酶2和二氢嘧啶脱氢酶的mRNA水平显著降低。在HCT-116细胞中，ID1抑制导致胸苷磷酸化酶、胸苷激酶和尿苷-胞苷激酶2的mRNA水平增加，同时二氢嘧啶脱氢酶和胸苷酸合成酶mRNA水平下降。总之，ID1表达影响结肠癌细胞对5-FU的敏感性，并可被视为CRC治疗中的潜在预测标志物。
Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for patients with advanced colorectal carcinoma. The major obstacle in successful treatment is the ability of CRC cells to acquire chemoresistance. Here we examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU. To suppress ID1 expression in HT-29 and HCT-116 cells the cells were transduced with a lentiviral vector carrying the ID1 silencing sequence. Cells with silenced ID1 showed altered expression of epithelial and mesenchymal markers and exhibited increased proliferation rate compared to the parental cells. HCT-116 cells with suppressed ID1 became sensitized to 5-FU and this was not observed in HT-29 cells. Silencing ID1 resulted in altered expression of genes encoding enzymes metabolizing 5-FU. HT-29 cells with suppressed ID1 had significantly reduced mRNA level for thymidine phosphorylase, uridine-cytydine kinase 2 and dihydropyrimidine dehydrogenase. ID1 suppression in HCT-116 cells resulted in an increase of mRNA level for thymidine phosphorylase, thymidine kinase and uridine-cytydine kinase 2 with concurrent drop of dihydropyrimidine dehydrogenase and thymidylate synthetase mRNA levels. In conclusion, ID1 expression impacts the sensitivity of colon cancer cells to 5-FU and may be considered as a potential predictive marker in CRC treatment.