腹腔镜下广泛子宫全切加盆腔淋巴结清扫术对子宫颈癌细胞凋亡率的影响及机制研究
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摘要
目的分析腹腔镜下广泛子宫全切加盆腔淋巴结清扫术对子宫颈癌细胞凋亡率的影响及其相关机制。方法选取2014年3月至2016年3月收治的子宫颈癌患者80例及子宫肌瘤患者40例作为研究对象。80例子宫颈癌患者,40例进行腹腔镜下广泛子宫全切加盆腔淋巴结清扫术,40例进行开腹广泛子宫全切加盆腔淋巴结清扫术。子宫肌瘤患者行腹腔镜全子宫切除术。采用流式细胞分析分别测定40例宫颈癌腹腔镜手术患者,手术前、后子宫颈癌细胞的凋亡率,并观察Trail、Bcl2、MTA1和NM23基因的表达水平,将其与腹腔镜下子宫全切术的正常子宫颈细胞和开腹手术的子宫颈癌细胞的手术前、后进行比较。结果子宫颈癌患者腹腔镜下治疗手术时间明显长于开腹治疗者(P<0.05),术中出血量、术后住院时间、胃肠道功能恢复时间明显短于开腹治疗者(P<0.05),术后并发症发生率与开腹手术者差异无统计学意义(P>0.05)。子宫颈癌细胞的术前凋亡率是(4.25±0.17)%,腹腔镜术后的凋亡率是(26.54±0.64)%,明显高于术前,差异有统计学意义(P<0.05);开腹手术后的凋亡率是(5.08±0.28)%,与术前相比,差异无统计学意义(P>0.05);子宫肌瘤患者术前的子宫颈细胞凋亡率是(18.26±0.46)%,腹腔镜术后的凋亡率是(17.36±0.57)%。行腹腔镜手术后的子宫颈癌细胞的抑制转移基因NM23和诱导凋亡基因Trail的表达水平明显比术前高,而相关转移基因MTA1和抑制凋亡基因Bcl2的表达水平则明显比术前低;正常的子宫颈细胞其相关基因Bcl2、MTA1、Trail和NM23的表达水平不受腹腔镜手术对机体的环境造成的变化而发生改变。结论采用腹腔镜手术治疗子宫颈癌不会增加癌细胞的增殖能力与转移能力,不增加术后并发症发生率,具有较好的临床有效性和安全性。
Objective To analyze the effects of total laparoscopic hysterectomy combined with pelvic lymphadenectomy on the apoptosis rate of cervical cancer cells and its related mechanisms. Methods Eighty patients with cervical cancer and 40 patients with uterine fibroids who were admitted and treated in our hospital from March 2014 to March2016 were enrolled in this study. Among the 80 patients with cervical cancer,40 patients underwent total laparoscopic hysterectomy combined with pelvic lymphadenectomy,whereas the other 40 patients underwent total abdominal hysterectomy combined with pelvic lymphadenectomy. The 40 patients with uterine fibroids were treated by laparoscopic hysterectomy. Flow cytometry was used to determine the apoptosis rate of cervical cancer cells before and after surgery in 40 patients with cervical cancer undergoing laparoscopic surgery. In addition,the expression levels of Trai L,Bcl2,MTA1,and NM23 genes were observed before and after laparoscopic hysterectomy,and compared with those in normal cervical cells before and after hysterectomy and those in cervical cancer cells before and after abdominal hysterectomy. Results The operation time in cervical cancer patients receiving laparoscopic hysterectomy was significantly longer than that in the patients receiving abdominal hysterectomy( P < 0. 05),however,the intraoperative blood loss,postoperative hospital stay and recovery time of gastrointestinal function in laparoscopic hysterectomy superior to those in abdominal hysterectomy( P < 0. 05). There were no significant differences in the incidence rates of postoperative complications between laparoscopic hysterectomy and abdominal hysterectomy( P > 0. 05). The preoperative apoptosis rate of cervical cancer cells was( 26. 54 ± 0. 64) %,which was significantly higher than that( 4. 2 ± 0. 17) % after laparoscopic surgery( P < 0. 05). The apoptotic rate was( 5. 08 ±0. 28) % after abdominal hysterectomy,as compared with that before surgery( P > 0. 05). The apoptosis rate of cervical cancer cells preoperatively was( 18. 26 ± 0. 46) % in patients with uterine leiomyoma,however,which was( 17. 36 ± 0. 57) %after laparoscopic surgery. The expression levels of the metastasis-inhibiting gene NM23 and the apoptotic gene Trail in cervical cancer cells were significantly increased after laparoscopic surgery,as compared with those before surgery,whereas the expression levels of metastasis-related gene MTA1 and the apoptosis-inhibiting gene Bcl2 were remarkably lower than those before surgery. Moreover the expression levels of Bcl2,MTA1,Trail,and NM23 in normal cervical cells did not vary with the changes in internal environm ent caused by laparoscopic surgery. Conclusion The laparoscopic hysterectomy for cervical cancer does not increase the proliferation and metastasis of cancer cells,or the incidence rate of postoperative complications,which suggests that the surgery method has excellent clinical efficacy and safety.
Objective To analyze the effects of total laparoscopic hysterectomy combined with pelvic lymphadenectomy on the apoptosis rate of cervical cancer cells and its related mechanisms. Methods Eighty patients with cervical cancer and 40 patients with uterine fibroids who were admitted and treated in our hospital from March 2014 to March2016 were enrolled in this study. Among the 80 patients with cervical cancer,40 patients underwent total laparoscopic hysterectomy combined with pelvic lymphadenectomy,whereas the other 40 patients underwent total abdominal hysterectomy combined with pelvic lymphadenectomy. The 40 patients with uterine fibroids were treated by laparoscopic hysterectomy. Flow cytometry was used to determine the apoptosis rate of cervical cancer cells before and after surgery in 40 patients with cervical cancer undergoing laparoscopic surgery. In addition,the expression levels of Trai L,Bcl2,MTA1,and NM23 genes were observed before and after laparoscopic hysterectomy,and compared with those in normal cervical cells before and after hysterectomy and those in cervical cancer cells before and after abdominal hysterectomy. Results The operation time in cervical cancer patients receiving laparoscopic hysterectomy was significantly longer than that in the patients receiving abdominal hysterectomy( P < 0. 05),however,the intraoperative blood loss,postoperative hospital stay and recovery time of gastrointestinal function in laparoscopic hysterectomy superior to those in abdominal hysterectomy( P < 0. 05). There were no significant differences in the incidence rates of postoperative complications between laparoscopic hysterectomy and abdominal hysterectomy( P > 0. 05). The preoperative apoptosis rate of cervical cancer cells was( 26. 54 ± 0. 64) %,which was significantly higher than that( 4. 2 ± 0. 17) % after laparoscopic surgery( P < 0. 05). The apoptotic rate was( 5. 08 ±0. 28) % after abdominal hysterectomy,as compared with that before surgery( P > 0. 05). The apoptosis rate of cervical cancer cells preoperatively was( 18. 26 ± 0. 46) % in patients with uterine leiomyoma,however,which was( 17. 36 ± 0. 57) %after laparoscopic surgery. The expression levels of the metastasis-inhibiting gene NM23 and the apoptotic gene Trail in cervical cancer cells were significantly increased after laparoscopic surgery,as compared with those before surgery,whereas the expression levels of metastasis-related gene MTA1 and the apoptosis-inhibiting gene Bcl2 were remarkably lower than those before surgery. Moreover the expression levels of Bcl2,MTA1,Trail,and NM23 in normal cervical cells did not vary with the changes in internal environm ent caused by laparoscopic surgery. Conclusion The laparoscopic hysterectomy for cervical cancer does not increase the proliferation and metastasis of cancer cells,or the incidence rate of postoperative complications,which suggests that the surgery method has excellent clinical efficacy and safety.
引文
1 Gien L,Bernardini M,Kupets R,et al.Is preoperative routine imaging useful for decision making in early stage cervical cancer?Gynecologic Oncology,2012,125:S63-S64.
2 Tergas A,Havrilesky L,Guntupalli S,et al.A cost analysis of colposcopy following abnormal cytology in post-treatment surveillance for cervical cancer.Gynecologic Oncology,2013,130:e55.
3 陈艳丽,李力.腹腔镜下宫颈癌根治术治疗早期宫颈癌的Meta分析.循证医学,2012,12:307-313.
4 Borhani N,Manoochehri M,Gargari SS,et al.Decreased expression of proapoptotic genes Caspase-8 and BCL2-associated agonist of cell death(BAD)in ovarian cancer.Clinical Ovarian and Other Gynecologic Cancer,2015,49:165-171.
5 宋英.腹腔镜手术治疗早期宫颈癌的效果分析.中国当代医药,2014,21:13-16.
6 伍永红,吴佩君.腹腔镜下手术治疗早期宫颈癌的临床效果分析.中国保健营养(上旬刊),2013,23:4225-4226.
7 范秀华,王康,邢艳超,等.悬吊式与传统腹腔镜子宫肌瘤挖除术的临床疗效对比.临床和实验医学杂志,2012,11:604-605,607.
8 潘爱容.腹腔镜治疗早期宫颈癌的临床效果分析.中国当代医药,2013,20:53-54.
9 孙秀丽.腹腔镜手术治疗早期子宫颈癌效果分析.中外健康文摘,2012,9:197-198.
10 Chou RH,Hsieh SC,Yu YL,et al.Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPKdependent NF-κB signaling pathway.Plo S one,2013,8:e71983.
11 Tewari KS,Monk BJ.New strategies in advanced cervical cancer:from angiogenesis blockade to immunotherapy.Clinical Cancer Research,2014,20:5349-5358.
12 李宏英,雷国庆,祝参,等.腹腔镜下广泛子宫切除加盆腔淋巴结清扫术与开腹手术的比较.中国实用医刊,2011,38:57-59.
13 朱巍立.腹腔镜下广泛子宫切除加盆腔淋巴结清扫术与开腹手术的比较.浙江创伤外科,2013,18:800-802.
14 黎勇明.腹腔镜下子宫根治术在治疗子宫恶性肿瘤的临床应用.中华全科医学,2013,11:1730-1731.
15 孔娜,冯爽,王玲,等.腹腔镜下广泛子宫切除及盆腔淋巴结清扫术治疗56例老年宫颈癌临床疗效分析.中国民族民间医药,2013,22:63-63.
16 杨晓瑞,葛静,周迪兰,等.七氟醚或丙泊酚复合瑞芬太尼麻醉在腹腔镜子宫切除术中的应用及对患者应激反应的影响.临床和实验医学杂志,2015,9:423-425,426.
17 彭佳琼.改良腹腔镜较大子宫切除术治疗较大子宫肌瘤95例临床观察.临床和实验医学杂志,2014,10:1727-1728.
18 尚贤文,王珺.腹腔镜手术对早期宫颈癌Suivivin表达的影响.中国内镜杂志,2013,19:489-491.
19 高翠玲.不同术式子宫肌瘤剔除术的疗效分析.临床和实验医学杂志,2012,11:211,213.
20 苏凤丽.经阴道子宫肌瘤剔除术与腹腔镜子宫肌瘤剔除术对比研究.临床和实验医学杂志,2012,11:867-868.
2 Tergas A,Havrilesky L,Guntupalli S,et al.A cost analysis of colposcopy following abnormal cytology in post-treatment surveillance for cervical cancer.Gynecologic Oncology,2013,130:e55.
3 陈艳丽,李力.腹腔镜下宫颈癌根治术治疗早期宫颈癌的Meta分析.循证医学,2012,12:307-313.
4 Borhani N,Manoochehri M,Gargari SS,et al.Decreased expression of proapoptotic genes Caspase-8 and BCL2-associated agonist of cell death(BAD)in ovarian cancer.Clinical Ovarian and Other Gynecologic Cancer,2015,49:165-171.
5 宋英.腹腔镜手术治疗早期宫颈癌的效果分析.中国当代医药,2014,21:13-16.
6 伍永红,吴佩君.腹腔镜下手术治疗早期宫颈癌的临床效果分析.中国保健营养(上旬刊),2013,23:4225-4226.
7 范秀华,王康,邢艳超,等.悬吊式与传统腹腔镜子宫肌瘤挖除术的临床疗效对比.临床和实验医学杂志,2012,11:604-605,607.
8 潘爱容.腹腔镜治疗早期宫颈癌的临床效果分析.中国当代医药,2013,20:53-54.
9 孙秀丽.腹腔镜手术治疗早期子宫颈癌效果分析.中外健康文摘,2012,9:197-198.
10 Chou RH,Hsieh SC,Yu YL,et al.Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPKdependent NF-κB signaling pathway.Plo S one,2013,8:e71983.
11 Tewari KS,Monk BJ.New strategies in advanced cervical cancer:from angiogenesis blockade to immunotherapy.Clinical Cancer Research,2014,20:5349-5358.
12 李宏英,雷国庆,祝参,等.腹腔镜下广泛子宫切除加盆腔淋巴结清扫术与开腹手术的比较.中国实用医刊,2011,38:57-59.
13 朱巍立.腹腔镜下广泛子宫切除加盆腔淋巴结清扫术与开腹手术的比较.浙江创伤外科,2013,18:800-802.
14 黎勇明.腹腔镜下子宫根治术在治疗子宫恶性肿瘤的临床应用.中华全科医学,2013,11:1730-1731.
15 孔娜,冯爽,王玲,等.腹腔镜下广泛子宫切除及盆腔淋巴结清扫术治疗56例老年宫颈癌临床疗效分析.中国民族民间医药,2013,22:63-63.
16 杨晓瑞,葛静,周迪兰,等.七氟醚或丙泊酚复合瑞芬太尼麻醉在腹腔镜子宫切除术中的应用及对患者应激反应的影响.临床和实验医学杂志,2015,9:423-425,426.
17 彭佳琼.改良腹腔镜较大子宫切除术治疗较大子宫肌瘤95例临床观察.临床和实验医学杂志,2014,10:1727-1728.
18 尚贤文,王珺.腹腔镜手术对早期宫颈癌Suivivin表达的影响.中国内镜杂志,2013,19:489-491.
19 高翠玲.不同术式子宫肌瘤剔除术的疗效分析.临床和实验医学杂志,2012,11:211,213.
20 苏凤丽.经阴道子宫肌瘤剔除术与腹腔镜子宫肌瘤剔除术对比研究.临床和实验医学杂志,2012,11:867-868.