Tang Hua, Liu Yuan-Jun, Liu Min, Li Xin
Tianjin Life Science Research Center, Tianjin Medical University, Tianjin, PRC.
Anticancer Drugs. 2007 Jul;18(6):633-9. doi: 10.1097/CAD.0b013e3280200428.
Oxaliplatin is widely used for chemotherapy of several malignancies, especially of colon cancer. As the mechanism of resistance to oxaliplatin is unclear, we established an oxaliplatin-resistant cell line, THC8307/L-OHP, from an oxaliplatin-sensitive colonic cancer cell line, THC8307. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay indicated that THC8307/L-OHP has 30.99-fold greater resistance to oxaliplatin than THC8307. Analyzing its gene expression profile using an in-house oligomicroarray, a number of genes were differentially expressed in the THC8307/L-OHP cells, compared with parental cells (THC8307). Proapoptotic genes such as STK17A and BNIP3 were significantly downregulated, whereas the genes PSAP and GDIA1, which were involved in antiapoptosis, were overexpressed. Moreover, the THC8307/L-OHP cells are also resistant to the other anticancer drug 5-fluorouracil, and the expression levels of the differentially regulated genes such as S100P, CAeta, STA15, TCF8 are constantly maintained. These results provide clues for understanding the oxaliplatin-resistant mechanisms and imply markers to predict drug sensitivities for 'personalized chemotherapy'.
奥沙利铂广泛用于多种恶性肿瘤的化疗，尤其是结肠癌。由于对奥沙利铂的耐药机制尚不清楚，我们从对奥沙利铂敏感的结肠癌细胞系THC8307建立了奥沙利铂耐药细胞系THC8307/L-OHP。噻唑蓝比色法检测表明，THC8307/L-OHP对奥沙利铂的耐药性是THC8307的30.99倍。使用自制的寡核苷酸微阵列分析其基因表达谱，与亲代细胞（THC8307）相比，THC8307/L-OHP细胞中有许多基因差异表达。促凋亡基因如STK17A和BNIP3显著下调，而参与抗凋亡的基因PSAP和GDIA1则过表达。此外，THC8307/L-OHP细胞对另一种抗癌药物5-氟尿嘧啶也有耐药性，并且差异调节基因如S100P、CAeta、STA15、TCF8的表达水平持续维持。这些结果为理解奥沙利铂耐药机制提供了线索，并暗示了预测“个体化化疗”药物敏感性的标志物。
