宫颈癌术前动脉灌注化疗对淋巴转移的影响及可能机制的研究

Preliminary study on the effect of arterial infusion chemotherapy before cervical cancer surgery on lymphatic metastasis and the possible action mechanism

目的分析术前动脉灌注化疗对宫颈癌的淋巴、脉管转移影响及化疗药物顺铂短时作用对宫颈癌Hela细胞黏附能力的影响,探讨宫颈癌术前动脉灌注化疗远期疗效不显著的原因。方法 722例宫颈鳞癌（腺癌）Ⅰb～Ⅱb患者按治疗方式分手术组和术前动脉灌注化疗后再行手术组,分别依据术后病理统计其淋巴结转移率及脉管内癌栓率。用含顺铂（0.05 mmol/L）的培液培养宫颈癌Hela细胞,分正常细胞组、顺铂持续作用组及顺铂短时作用后撤药组,于不同时间点收集细胞,用real-time PCR染料法定量测定宫颈癌细胞黏附因子CD44表达的改变。结果宫颈癌术前动脉内灌注化疗后再行手术的肿瘤脉管内癌栓发生率低于直接手术组,淋巴转移率高于直接手术组（P〈0.05）。顺铂的持续药物作用能降低Hela细胞CD44的表达;顺铂短时作用撤除后,CD44表达水平高于正常Hela细胞组和顺铂持续作用组,并且波动幅度增大。结论宫颈癌术前动脉灌注化疗可能增加宫颈癌转移的风险,而化疗药物顺铂短时作用后,细胞黏附因子CD44表达的升高及波动幅度的增大,提示其可能促进残留肿瘤细胞脱落、迁移和定居,与宫颈癌术前灌注化疗增加淋巴转移率可能相关。

Objective To investigate the effect of arterial infusion chemotherapy before cervical cancer surgery on lymphatic vessel metastasis and the short time effect of cisplatin on adhesion ability of cervical cancer Hela cells,and to explore the prostecdtive efficacy of arterial infusion chemotherapy before cervical cancer surgery.Methods Seven hundred and twenty-two patients with cervical cancer Ⅰb ～ Ⅱb were divided into direct operation group and observation group in which the operation was performed after arterial infusion chemotherapy.The lymph node metastasis rate and cancer embolism rate in vessel were calculated according to postoperative pathological examination.The Hela cells were cultured in the medium with cisplatin（0.05 mmol / L）,which were divided into normal control group,cisplatin persistent effect group,cisplatin short time effect group,finally,the cells were collected in different time points,then the changes of cervical cancer cell adhesion factor-CD44 were detected by Real-time PCR.Results The cancer embolism rate in tumor vessel in observation group was significantly lower than that in direct operation group,however,the lymph node metastasis rate in observation group was significantly higher than that in direct operation group（P〈0.05）.The cisplatin persistent effect could decrease the expression levels of CD44 in Hela cells,however,the expression levels of CD44 in cisplatin short time effect group were significantly higher than those in normal control group and in cisplatin persistent effect group.Conclusion The arterial infusion chemotherapy before cervical cancer surgery may increase the risk of cervical cancer metastasis,moreover,after short time effect by cisplatin,the expression levels of CD44 and its fluctuation extent are increased,which suggests that it may promote residual tumor cells＇ exfoliation,migration and settle-down and may be correlated to the increase of lymph node metastasis rate caused by arterial infusion chemotherapy before cervical cancer surgery.