沙利度胺对宫颈癌裸鼠移植瘤的放疗增敏作用及其机制研究
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摘要
目的探讨沙利度胺对宫颈癌裸鼠移植瘤的放疗增敏作用及其可能的作用机制。方法将0.2ml悬浊液(1×10~7/ml人宫颈癌Hela细胞)接种于20只BALB/c裸鼠,1周后成瘤,采用随机数字表法分为对照组、沙利度胺组、单纯放疗组(20Gy组)和沙利度胺联合放疗组(沙利度胺+20Gy组)4组,每组5只。对照组:腹腔注射0.2ml 0.5%羧甲基纤维钠,1次/d,连续14d;沙利度胺组:腹腔注射0.2ml沙利度胺溶液,1次/d,连续14d;20Gy组:用6MVX线照射移植瘤瘤体,2Gy/d,5次/周,共10次;沙利度胺+20Gy组:腹腔注射0.2ml沙利度胺溶液,1次/d,连续14d,放疗措施同20Gy组。各组每2d测量1次肿瘤体积,2周后剥瘤称重,计算抑瘤率。采用免疫组化SABC法测定移植瘤组织中血管内皮生长因子(VEGF)的表达情况。结果与对照组比较,沙利度胺组、20Gy组、沙利度胺+20Gy组肿瘤体积和瘤重均明显下降,抑瘤率均明显上升,差异均有统计学意义(均P<0.05)。与沙利度胺组、20Gy组比较,沙利度胺+20Gy组肿瘤体积和瘤重均明显下降,抑瘤率均明显上升,差异均有统计学意义(均P<0.05)。对照组、沙利度胺组、20Gy组和沙利度胺+20Gy组裸鼠移植瘤组织中VEGF表达分别呈强阳性、阳性、阳性和弱阳性,后3组与对照组相比VEGF表达均下降,其中沙利度胺+20Gy组下降最明显。结论沙利度胺能增强人宫颈癌裸鼠移植瘤对放疗的敏感性,其机制可能与抑制移植瘤VEGF的生成有关。
Objective To investigate the effect of thalidomide on radiotherapy sensitization in nude mice with cervical carcinoma and its mechanism. Methods Twenty BALB/c nude mice were inoculated with 0.2 ml suspension(1×10~7/ml human cervical cancer Hela cells), and were randomly divided into control group, thalidomide group(TLD group), radiotherapy alone group(20 Gy group) and thalidomide combined radiotherapy group(TLD +20 Gy group) after tumor formation for 1 week, 5 mice in each group. In control group 0.2 ml 0.5% carboxymethyl sodium fiber was injected intraperitoneally 1/d for 14 d. In TLD group 0.2 ml thalidomide was intraperitoneally injected 1/d for 14 d. In 20 Gy group 6 MVX-ray irradiation was given to transplant tumor, 2 Gy/d, 5/wk for 2 wks. In TLD+20 Gy group intraperitoneal injection of 0.2 ml thalidomide for 14 d, and concurrent radiotherapy for 10 times. Tumor volume was measured every 2 d, and tumor weight was measured 2 wks later to calculate the tumor inhibition rate. The expression of vascular endothelial growth factor(VEGF) in transplanted tumor tissues was determined by immunohistochemical SABC assay.Results Compared with the control group, the tumor volume and tumor weight of TLD group, 20 Gy group and TLD+20 Gy group were significantly decreased(all P<0.05). Compared with the TLD group and the 20 Gy group, the tumor volume and tumor weight in the TLD+20 Gy group was significantly lower, and the tumor inhibition rate was significantly higher(all P<0.05). VEGF expression in tumor tissue of the control group, TLD group, 20 Gy group and TLD+20 Gy group showed strong positive, positive, positive and weak positive, respectively. Compared with the control group, VEGF expression in the latter three groups all decreased, and that in TLD+20 Gy group was lowest. Conclusion Thalidomide can enhance the sensitivity of human cervical cancer xenograft tumor to radiotherapy in nude mice, which may be related to the inhibition of VEGF expression.
Objective To investigate the effect of thalidomide on radiotherapy sensitization in nude mice with cervical carcinoma and its mechanism. Methods Twenty BALB/c nude mice were inoculated with 0.2 ml suspension(1×10~7/ml human cervical cancer Hela cells), and were randomly divided into control group, thalidomide group(TLD group), radiotherapy alone group(20 Gy group) and thalidomide combined radiotherapy group(TLD +20 Gy group) after tumor formation for 1 week, 5 mice in each group. In control group 0.2 ml 0.5% carboxymethyl sodium fiber was injected intraperitoneally 1/d for 14 d. In TLD group 0.2 ml thalidomide was intraperitoneally injected 1/d for 14 d. In 20 Gy group 6 MVX-ray irradiation was given to transplant tumor, 2 Gy/d, 5/wk for 2 wks. In TLD+20 Gy group intraperitoneal injection of 0.2 ml thalidomide for 14 d, and concurrent radiotherapy for 10 times. Tumor volume was measured every 2 d, and tumor weight was measured 2 wks later to calculate the tumor inhibition rate. The expression of vascular endothelial growth factor(VEGF) in transplanted tumor tissues was determined by immunohistochemical SABC assay.Results Compared with the control group, the tumor volume and tumor weight of TLD group, 20 Gy group and TLD+20 Gy group were significantly decreased(all P<0.05). Compared with the TLD group and the 20 Gy group, the tumor volume and tumor weight in the TLD+20 Gy group was significantly lower, and the tumor inhibition rate was significantly higher(all P<0.05). VEGF expression in tumor tissue of the control group, TLD group, 20 Gy group and TLD+20 Gy group showed strong positive, positive, positive and weak positive, respectively. Compared with the control group, VEGF expression in the latter three groups all decreased, and that in TLD+20 Gy group was lowest. Conclusion Thalidomide can enhance the sensitivity of human cervical cancer xenograft tumor to radiotherapy in nude mice, which may be related to the inhibition of VEGF expression.
引文
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[9]陈宓.沙利度胺联合同步放化疗治疗局部晚期鼻咽癌临床观察[J].现代医药卫生,2017,33(3):360-363.DOI:10.3969/j.issn.1009-5519.2017.03.014.
[10]夏一丹,谢兰,何文静,等.HIF-1α和VEGF在宫颈癌变过程中的表达及临床意义[J].医学理论与实践,2018,31(1):18-20,23.DOI:10.19381/j.issn.1001-7585.2018.01.007.
[11]杨建刚,陈继正,赵参军,等.沙利度胺在治疗晚期实体肿瘤中的应用及研究进展[J].现代肿瘤医学,2017,25(11):1805-1809.DOI:10.3969/j.issn.1672-4992.2017.11.036.
[12]杜娟.沙利度胺对卵巢癌的化疗前景[J].现代肿瘤医学杂志,2013,21(12):2850-2853.DOI:10.3969/j.issn.1672-4992.2013.12.71.
[13]雷蕾,王娴,王晓稼.沙利度胺治疗常见非血液系统肿瘤的研究进展[J].国际肿瘤学杂志,2017,43(9):711-714.DOI:10.3760/cma.j.issn.1673-422X.2016.09.018.
[14]Davis M,Lasheen W,Walsh D,et al.A PhaseⅡDose Titration Study of Thalidomide for Camcer-Associated Anorexia[J].Journal of Pain and Symptom Manage,2012,43(1):78-86.DOI:10.1016/j.jpainsymman.2011.03.007.
[2]Ghose S,Holloway L,LIn K,et al.A review of segmen-tation and deformable registration methods applied to adaptive cervical cancer radiation therapy treatment planning[J].Artif Intell Med,2015,64(2):75.DOI:10.1016/j.artmed.2015.04.006.
[3]于静萍,孙志强,倪新初,等.沙利度胺联合照射对人食管癌裸鼠移植瘤生长和肿瘤血管生成的影响[J].中华放射医学与防护杂志,2013,33(6):584-587.DOI:10.3760/cma.j.issn.0254-5098.2013.06.004.
[4]赵瑾,韩立杰,赵悦,等.沙利度胺联合放射治疗对结肠癌小鼠移植瘤生长及放射敏感性的影响[J].中国癌症杂志,2014,24(3):170-174.DOI:10.3969/j.issn.1007-3969.2014.03.003.
[5]Li Y,Chu Y,Song R,et al.Thalidomide combined with chemotherapy in treating elderly patients with advance dgastric cancer[J].Aging clinical and experimental research,2018,30(5):499-505.DOI:10.1007/s40520-017-0790-z.
[6]陈德连,陈明聪,江会红.大剂量维生素B6联合阿帕替尼治疗晚期非小细胞肺癌的疗效观察[J].浙江医学,2018,40(3):291-293.DOI:10.12056/j.issn.1006-2785.2017.40.3.2017-594.
[7]黄海宁,张浩,汪海,等.沙利度胺抗肿瘤机制及其作用靶点CRBN的研究进展[J].中国药理学通报,2015,31(6):745-748,749.DOI:10.3969/j.issn.1001-1978.2015.06.002.
[8]董志强.沙利度胺联合放射治疗治疗食管癌的临床疗效观察[J].中国肿瘤临床与康复杂志,2014,21(9):1094-1096.DOI:10.13455/j.cnki.cjcor.2014.09.24.
[9]陈宓.沙利度胺联合同步放化疗治疗局部晚期鼻咽癌临床观察[J].现代医药卫生,2017,33(3):360-363.DOI:10.3969/j.issn.1009-5519.2017.03.014.
[10]夏一丹,谢兰,何文静,等.HIF-1α和VEGF在宫颈癌变过程中的表达及临床意义[J].医学理论与实践,2018,31(1):18-20,23.DOI:10.19381/j.issn.1001-7585.2018.01.007.
[11]杨建刚,陈继正,赵参军,等.沙利度胺在治疗晚期实体肿瘤中的应用及研究进展[J].现代肿瘤医学,2017,25(11):1805-1809.DOI:10.3969/j.issn.1672-4992.2017.11.036.
[12]杜娟.沙利度胺对卵巢癌的化疗前景[J].现代肿瘤医学杂志,2013,21(12):2850-2853.DOI:10.3969/j.issn.1672-4992.2013.12.71.
[13]雷蕾,王娴,王晓稼.沙利度胺治疗常见非血液系统肿瘤的研究进展[J].国际肿瘤学杂志,2017,43(9):711-714.DOI:10.3760/cma.j.issn.1673-422X.2016.09.018.
[14]Davis M,Lasheen W,Walsh D,et al.A PhaseⅡDose Titration Study of Thalidomide for Camcer-Associated Anorexia[J].Journal of Pain and Symptom Manage,2012,43(1):78-86.DOI:10.1016/j.jpainsymman.2011.03.007.