Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells
Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells
复制标题
结直肠癌细胞中 PTEN 破坏增强姜黄素细胞毒性
DOI：
10.3748/wjg.v19.i40.6814
复制
发表时间：
2013-10-28
影响因子：
4.3
通讯作者：
Lu, Xin-Cheng
中科院分区：
文献类型：
--
作者：
Chen, Lin;Li, Wen-Feng;Lu, Xin-Cheng
目的：探讨10号染色体上缺失的磷酸酶和张力蛋白同源缺失(PTEN)基因缺失对化疗药物对结直肠癌细胞杀伤作用的影响。用四甲基偶氮唑盐比色法测定姜黄素、5-氟尿嘧啶(5-FU)、双氢青蒿素(DHA)、伊立替康(CPT-11)和奥沙利铂(OXA)对癌细胞的杀伤作用。在PTEN缺陷的CRC细胞中，观察到姜黄素增强了细胞毒性，克隆形成实验证实了这一点。流式细胞仪检测细胞凋亡和细胞周期进程。用Western blotting检测细胞凋亡和细胞周期相关蛋白的水平。结果：我们建立了一组相同基因的结直肠癌细胞株，只是它们的PTEN状态不同。利用这一组细胞系，我们发现PTEN基因的破坏对结直肠癌细胞对5-FU、CPT-11、DHA或OXA的敏感性没有影响，而PTEN基因的破坏增加了结直肠癌细胞对姜黄素的敏感性。PTEN的缺失不能改变姜黄素诱导的大肠癌细胞的凋亡。然而，PTEN缺失导致了姜黄素介导的细胞周期停滞模式的改变。在HCT116 PTEN+/+细胞中，姜黄素引起G2/M期阻滞，而在HCT116 PTEN-/-细胞中，姜黄素引起G0/G1期阻滞。结论：姜黄素对PTEN基因缺陷的肿瘤细胞具有较强的细胞毒作用，有望成为治疗PTEN基因突变肿瘤的潜在化疗药物。(C)2013年白石登。版权所有。
AIM: To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency on the cytotoxicity of chemotherapeutic agents toward colorectal cancer cells.METHODS: PTEN-deficient colorectal cancer (CRC) cells were generated by human somatic cell gene targeting using the adeno-associated virus system. The cytotoxic effects of compounds including curcumin, 5-fluorouracil (5-FU), dihydroartemisinin (DHA), irinotecan (CPT-11) and oxaliplatin (OXA) on cancer cells were determined using the MTT assay. Enhanced cytotoxicity of curcumin in PTEN-deficient CRC cells was observed, and this was confirmed using clonogenic assays. Apoptosis and cell cycle progression were analyzed by flow cytometry. Levels of apoptosis and cell cycle-related proteins were examined by Western blotting.RESULTS: We developed an isogenic set of CRC cell lines that differed only in their PTEN status. Using this set of cell lines, we found that disruption of the PTEN gene had no effect on the sensitivity of CRC cells to 5-FU, CPT-11, DHA, or OXA, whereas PTEN disruption increased the sensitivity of CRC cells to curcumin. Loss of PTEN did not alter the curcumin-induced apoptosis in CRC cells. However, PTEN deficiency led to an altered pattern of curcumin-mediated cell cycle arrest. In HCT116 PTEN+/+ cells, curcumin caused a G2/M phase arrest, whereas it caused a G0/G1 phase arrest in HCT116 PTEN-/- cells. Levels of cell cycle-related proteins were consistent with these respective patterns of cell cycle arrest.CONCLUSION: Curcumin shows enhanced cytotoxicity toward PTEN-deficient cancer cells, suggesting that it might be a potential chemotherapeutic agent for cancers harboring PTEN mutations. (C) 2013 Baishideng. All rights reserved.