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目的:评估余甘子提取物(PE)对丝裂霉素C(MMC)和顺铂(cDDP)抗癌活性及其遗传毒性副作用的影响。创新点:首次发现PE能减弱MMC和cDDP对人正常结肠上皮细胞基因组的损伤以及降低基因组受损细胞的克隆形成能力和克隆异质性。方法:人结肠癌Colo205细胞和人正常结肠上皮NCM460细胞分别经PE、PE+MMC组合或PE+cDDP组合处理72 h。细胞增殖用台盼蓝拒染法和克隆形成法测定,遗传毒性用胞质分裂阻断微核分析法(CBMN)测定。结论:结果显示,PE可以显著增强MMC和cDDP的抗Colo205细胞增殖能力(图1)。同时,PE显著降低MMC和cDDP诱导的NCM460细胞基因组不稳定现象,包括降低微核、核质桥和核芽(表1和图2)以及多核化细胞(图3)。此外,PE显著降低经MMC和cDDP处理的NCM460细胞克隆性扩增能力,并降低克隆的异质性(图4)。综上所述,PE不仅能增强MMC和cDDP的抗癌能力,还可能具有减弱它们诱发正常细胞恶性转变的潜力。
Objective: To evaluate the effect of Phyllanthus emblica extract on the anticancer activity and genotoxicity of mitomycin C (MMC) and cisplatin (cDDP). Innovative point: PE was found for the first time to attenuate MMC and cDDP damage to human normal colonic epithelial cell genome and to reduce clonogenic capacity and clonal heterogeneity of genomic impaired cells. METHODS: Human colon cancer Colo205 cells and normal human colorectal epithelial NCM460 cells were treated with PE, PE + MMC or PE + cDDP for 72 h. Cell proliferation was determined by trypan blue exclusion and clonogenic assay, and genotoxicity was assayed by the cytokinesis-block micronucleus assay (CBMN). Conclusion: The results show that PE can significantly enhance the proliferation of MMC and cDDP against Colo205 cells (Figure 1). At the same time, PE significantly reduced the genomic instability of NCM460 cells induced by MMC and cDDP, including micronuclei, nucleoplasm bridges and nuclear buds (Table 1 and Figure 2) and multinucleated cells (Figure 3). In addition, PE significantly decreased clonality in NCM460 cells treated with MMC and cDDP, and decreased clonal heterogeneity (Figure 4). In summary, PE not only enhances the anticancer ability of MMC and cDDP, but may also have the potential to reduce their potential for inducing malignant transformation in normal cells.