组蛋白去乙酰化酶抑制剂 CG2 联合伊立替康、5-氟尿嘧啶或奥沙利铂对 HCT116 结肠癌细胞及其异种移植瘤的影响。

Effects of the HDAC inhibitor CG2 in combination with irinotecan, 5-fluorouracil, or oxaliplatin on HCT116 colon cancer cells and xenografts.

机构信息

Institute for Innovate Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Oncol Rep. 2010 Dec;24(6):1509-14. doi: 10.3892/or_00001012.

DOI:10.3892/or_00001012

PMID:21042746

Abstract

Chemotherapies for colon cancer have recently advanced. However, there is still a need to develop agents and identify effective regimens for better treatments of colon cancer. Histone deacetylase inhibitors (HDACIs) have shown potential as anti-cancer agents. We investigated the anti-tumor effects of CG2 (an HDACI) in combination with irinotecan, 5-FU, or oxaliplatin. Combinations of CG2 with SN38 (the active form of irinotecan), 5FU, or oxaliplatin were more effective than the agents alone when used to inhibit the growth of HCT116 cells. The protein expressions of acetyl-H3, p21, caspase-3, -8, and -9, PARP, and XIAP were affected in a time- and dose-dependent manner in HCT116 cells treated with the CG2 alone or combined CG2 and SN-38. In HCT116 xenografts, the HDACI CG2 in combination with irinotecan dramatically inhibited tumor growth without showing additive toxicity. These data indicate that CG2 together with irinotecan is a promising combination novel treatment for colon cancer.

摘要

结肠癌的化疗最近取得了进展。然而，仍然需要开发新的药物并确定有效的方案，以更好地治疗结肠癌。组蛋白去乙酰化酶抑制剂（HDACIs）已显示出作为抗癌药物的潜力。我们研究了 CG2（一种 HDACI）与伊立替康、5-FU 或奥沙利铂联合使用的抗肿瘤作用。CG2 与 SN38（伊立替康的活性形式）、5FU 或奥沙利铂联合使用时，在抑制 HCT116 细胞生长方面比单独使用这些药物更有效。用 CG2 单独或与 CG2 和 SN-38 联合处理 HCT116 细胞时，乙酰化 H3、p21、caspase-3、-8 和 -9、PARP 和 XIAP 的蛋白表达呈时间和剂量依赖性。在 HCT116 异种移植瘤中，HDACI CG2 联合伊立替康显著抑制肿瘤生长，而没有表现出附加毒性。这些数据表明，CG2 联合伊立替康是一种有前途的结肠癌联合治疗新方法。