Liang Hua, Yang Chengxiang, Zhang Bin, Wang Hanbing, Liu Hongzhen, Zhao Zhenlong, Zhang Zhiming, Wen Xianjie, Lai Xiaohong
Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, Foshan, 528000, China,
Med Oncol. 2015 May;32(5):151. doi: 10.1007/s12032-015-0601-3. Epub 2015 Apr 2.
Platelets play an important role in metastasis of circulating tumor cells (CTCs). It has been demonstrated that hydroxyethyl starch (HES) inhibits platelets function. However, the effect of HES on CTCs in patients with colorectal cancer remains unclear. We compared the effects of HES 200/0.5 and HES 130/0.4 on CTCs and platelets activation of colorectal patients in this study. Additionally, the effects of HES 200/0.5 or HES 130/0.4 on metastasis ability of colon cancer cell line that stimulated by activated platelets have been explored. In vivo, 90 patients undergoing colorectal cancer radical surgery received randomly 15 mL/kg of HES 200/0.5 (n = 45) or HES 130/0.4 (n = 45) infusion before surgery. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa), CD62P and platelets aggregation rate (PAR) were evaluated pre-, intra- and postoperatively. Cytokeratin-20 (CK-20) mRNA was detected by reverse transcriptase polymerase chain reaction before and after surgery. In vitro, colon cancer SW480 cells were incubated with activated platelets in the presence or absence HES 200/0.5 or HES 130/0.4. The metastasis ability of SW480 cells was assessed by Transwell assay. The results showed that CK-20 mRNA positive rate in HES 200/0.5 group after surgery was decreased significantly as compared to group HES 130/0.4 (χ (2) = 6.164, P = 0.013). Simultaneously, a more pronounced inhibition of platelets activation was observed in group HES 200/0.5. A positive correlation between platelets activation marker and CK-20 mRNA positive rate was found. In vitro, HES 200/0.5, but not HES 130/0.4, decreased the invasion and migration ability of SW480 cells that induced by activated platelets. Besides, the expression of GPIIb/IIIa, CD62P and PAR was inhibited more strongly in group HES 200/0.5 than those in group HES 130/0.4. In summary, we found that HES 200/0.5 significantly decreased CTCs of patients undergoing colorectal cancer radical surgery as compared to HES 130/0.4, which might be associated with inhibiting platelets activation of HES 200/0.5. Furthermore, HES 200/0.5, but not HES 130/0.4, reduced the metastatic potential of colon cell line stimulated by activated platelets through depressing platelets activation. Modulation of platelets activity may be a novel strategy to minimize the risk of metastasis during surgery.
血小板在循环肿瘤细胞(CTC)的转移中起重要作用。已经证明羟乙基淀粉(HES)可抑制血小板功能。然而,HES对结直肠癌患者循环肿瘤细胞的影响仍不清楚。在本研究中,我们比较了HES 200/0.5和HES 130/0.4对结直肠癌患者循环肿瘤细胞和血小板活化的影响。此外,还探讨了HES 200/0.5或HES 130/0.4对由活化血小板刺激的结肠癌细胞系转移能力的影响。在体内,90例行结直肠癌根治术的患者在手术前随机接受15 mL/kg的HES 200/0.5(n = 45)或HES 130/0.4(n = 45)输注。在术前、术中和术后评估血小板糖蛋白IIb/IIIa(GPIIb/IIIa)、CD62P和血小板聚集率(PAR)。通过逆转录聚合酶链反应在手术前后检测细胞角蛋白-20(CK-20)mRNA。在体外,将结肠癌细胞SW480与活化血小板在有或无HES 200/0.5或HES 130/0.4的情况下孵育。通过Transwell试验评估SW480细胞的转移能力。结果显示,与HES 130/0.4组相比,HES 200/0.5组术后CK-20 mRNA阳性率显著降低(χ(2)= 6.164,P = 0.013)。同时,在HES 200/0.5组中观察到对血小板活化的抑制作用更明显。发现血小板活化标志物与CK-20 mRNA阳性率之间呈正相关。在体外,HES 200/0.5而非HES 130/0.4降低了由活化血小板诱导的SW480细胞的侵袭和迁移能力。此外,HES 200/0.5组中GPIIb/IIIa、CD62P和PAR的表达受到的抑制比HES 130/0.4组更强。总之,我们发现与HES 130/0.4相比,HES 200/0.5显著降低了行结直肠癌根治术患者的循环肿瘤细胞,这可能与HES 200/0.5抑制血小板活化有关。此外,HES 200/0.5而非HES 130/0.4通过抑制血小板活化降低了由活化血小板刺激的结肠癌细胞系的转移潜能。调节血小板活性可能是降低手术期间转移风险的一种新策略。