Erdmann Kati, Ringel Jessica, Hampel Silke, Rieger Christiane, Huebner Doreen, Wirth Manfred P, Fuessel Susanne
Nanotechnology. 2014 Oct 10;25(40):405102. doi: 10.1088/0957-4484/25/40/405102.
Recent studies have shown that carbon nanomaterials such as carbon nanofibres (CNFs) and multi-walled carbon nanotubes (CNTs) can exert antitumor activities themselves and sensitize cancer cells to conventional chemotherapeutics such as carboplatin and cisplatin. In the present study, the chemosensitizing effect of CNFs and CNTs on cancer cells of urological origin was investigated regarding the underlying mechanisms. Prostate cancer (DU-145, PC-3) and bladder cancer (EJ28) cells were treated with carbon nanomaterials (CNFs, CNTs) and chemotherapeutics (carboplatin, cisplatin) alone as well as in combination for 24 h. Forty-eight(EJ28) or 72 h (DU-145, PC-3) after the end of treatment the effects on cellular proliferation,clonogenic survival, cell death rate and cell cycle distribution were evaluated. Depending on the cell line, simultaneous administration of chemotherapeutics and carbon nanomaterials produced an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98%, respectively, compared to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced antiproliferative effects were accompanied by an elevated cell death rate, which was predominantly mediated via apoptosis and not by necrosis. The antitumor effects of combinations with CNTs were less pronounced than those with CNFs. The enhanced effects of the combinatory treatments on cellular function were mostly of additive to partly synergistic nature. Furthermore, cell cycle analysis demonstrated an arrest at the G2/M phase mediated by a monotreatment with chemotherapeutics. Following combinatory treatments, mostly less than or nearly additive increases of cell fractions in the G2/M phase could be observed. In conclusion,the pronounced chemosensitizing effects of CNFs and CNTs were mediated by an enhanced apoptosis and inhibition of proliferation. The combination of carbon-based nanomaterials and conventional chemotherapeutics represents a novel approach in cancer therapy to bypass chemoresistance by minimizing the chemotherapeutic dosing.
最近的研究表明，碳纳米纤维（CNFs）和多壁碳纳米管（CNTs）等碳纳米材料自身可发挥抗肿瘤活性，并使癌细胞对卡铂和顺铂等传统化疗药物敏感。在本研究中，针对潜在机制研究了CNFs和CNTs对泌尿生殖系统来源癌细胞的化学增敏作用。前列腺癌（DU-145、PC-3）和膀胱癌（EJ28）细胞分别单独以及联合使用碳纳米材料（CNFs、CNTs）和化疗药物（卡铂、顺铂）处理24小时。处理结束后48小时（EJ28）或72小时（DU-145、PC-3），评估对细胞增殖、克隆形成存活率、细胞死亡率和细胞周期分布的影响。根据细胞系不同，与单独使用化疗药物的抑制作用相比，同时给予化疗药物和碳纳米材料分别对细胞增殖和克隆形成存活率产生了高达77%和98%的额外抑制作用。这些显著增强的抗增殖作用伴随着细胞死亡率升高，其主要通过凋亡而非坏死介导。与CNFs联合使用相比，与CNTs联合使用的抗肿瘤作用不太明显。联合治疗对细胞功能增强的作用大多为相加至部分协同性质。此外，细胞周期分析表明，单独使用化疗药物处理可介导细胞在G2/M期停滞。联合治疗后，大多观察到G2/M期细胞比例增加小于或接近相加水平。总之，CNFs和CNTs显著的化学增敏作用是由凋亡增强和增殖抑制介导的。碳基纳米材料与传统化疗药物的联合使用代表了癌症治疗中的一种新方法，可通过最小化化疗药物剂量来绕过化疗耐药性。
