Department of General Surgery, Peking Union Medical College Hospital, National Laboratory of Medical Molecular Biology, Chinese Academy of Medial Sciences and Peking Union Medical College, Beijing 100730, China.
Chin Med J (Engl). 2011 Feb;124(3):419-22.
Single nucleotide polymorphisms (SNPs) in the deoxycytidine kinase (dCK) gene are associated with chemosensitivity to nucleoside analogs. 2',2'-Difluoro 2'-deoxycytidine (gemcitabine) is a first-line nucleoside analog drug in the treatment of pancreatic cancer. However, the association between SNPs in the dCK gene and chemosensitivity to gemcitabine has not been fully established. Therefore, the present study aimed to investigate the relationship between SNPs in the dCK gene and chemosensitivity to gemcitabine in human pancreatic cancer cell lines.
Seven SNPs in the dCK gene were sequenced in six human pancreatic cancer cell lines. The chemosensitivity of these six cell lines to gemcitabine were evaluated in vitro with a Cell Counting Kit-8 (CCK-8) test. Inhibition rates were used to express the chemosensitivity of pancreatic cancer cell lines to gemcitabine.
The genotype of the A9846G SNP in the dCK gene was determined in six human pancreatic cancer cell lines. The cell lines BxPC-3 and T3M4 carried the A9846G SNP genotype AG, whereas cell lines AsPC-1, Mia PaCa2, SW1990 and SU86.86 carried the GG genotype. Cell lines with the AG genotype (BxPC-3 and T3M4) were more sensitive to gemcitabine compared with cell lines with the GG genotype (AsPC-1, Mia PaCa2, SW1990 and SU86.86) and significantly different inhibition rates were observed between cell lines carrying the AG and GG genotypes (P < 0.01).
Variants in the A9846G SNP of the dCK gene were associated with sensitivity to gemcitabine in pancreatic cancer cell lines. The dCK A9846G SNP may act as a genetic marker to predict chemotherapy efficacy of gemcitabine in pancreatic cancer.
脱氧胞苷激酶 (dCK) 基因中的单核苷酸多态性 (SNP) 与核苷类似物的化疗敏感性相关。2',2'-二氟-2'-脱氧胞苷 (吉西他滨) 是治疗胰腺癌的一线核苷类似物药物。然而，dCK 基因中的 SNP 与吉西他滨化疗敏感性之间的关系尚未完全确定。因此，本研究旨在探讨人胰腺癌细胞系中 dCK 基因 SNP 与吉西他滨化疗敏感性的关系。
对 6 个人胰腺癌细胞系中的 7 个 dCK 基因 SNP 进行测序。采用 Cell Counting Kit-8 (CCK-8) 试验体外评估这 6 个细胞系对吉西他滨的化疗敏感性。抑制率用于表示胰腺癌细胞系对吉西他滨的化疗敏感性。
在 6 个人胰腺癌细胞系中确定了 dCK 基因 A9846G SNP 的基因型。细胞系 BxPC-3 和 T3M4 携带 A9846G SNP 基因型 AG，而细胞系 AsPC-1、Mia PaCa2、SW1990 和 SU86.86 携带 GG 基因型。AG 基因型（BxPC-3 和 T3M4）的细胞系对吉西他滨更敏感，而 GG 基因型（AsPC-1、Mia PaCa2、SW1990 和 SU86.86）的细胞系对吉西他滨更不敏感，携带 AG 和 GG 基因型的细胞系之间观察到明显不同的抑制率（P < 0.01）。
dCK 基因 A9846G SNP 变体与胰腺癌细胞系对吉西他滨的敏感性相关。dCK A9846G SNP 可能作为遗传标记预测胰腺癌吉西他滨化疗疗效。
