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| 纳洛酮复合吗啡对裸鼠人胃癌皮下瘤生长的影响 |
| Effect of naloxone in combination with morphine on the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice |
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| DOI： |
| 中文关键词: 吗啡 纳洛酮 胃癌 皮下瘤 |
| 英文关键词: Morphine Naloxone Gastric cancer Subcutaneous tumor |
| 基金项目:国家自然科学基金(81560500,81160289);广西自然科学基金（2013GXNSFBA019156）;广西科学研究与技术开发计划课题（桂科攻1355005-1-6） |
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| 中文摘要: |
| 目的 观察纳洛酮复合吗啡对裸鼠人胃癌皮下瘤生长的影响。方法 建立裸鼠人胃癌MGC-803细胞皮下瘤模型,将50只裸鼠随机分为五组:对照组(C组)、生理盐水组(S组)、20 mg／kg 吗啡组(M组)、1 mg／kg纳洛酮组(N组)、1 mg／kg纳洛酮+20 mg／kg 吗啡组(NM组),每组10只。成瘤后,C组不作任何处理;S、M、N组裸鼠每天在右下腹分别腹腔注射生理盐水1.5 ml／kg、吗啡20 mg／kg或纳洛酮1 mg／kg;NM组裸鼠每天在右下腹先腹腔注射纳洛酮1 mg／kg,30 min后再给予吗啡20 mg／kg;连续注射14 d。每2天测量1次肿瘤的长径和短径,计算肿瘤相对体积(RTV);用药结束后拉颈处死裸鼠,采用透射电镜观察肿瘤组织的结构变化,免疫组化、半定量逆转录-聚合酶链反应(RT-PCR)和Western blot法检测肿瘤组织中Cyclin D1、血管内皮生长因子(VEGF)、基质金属蛋白酶9（MMP-9）的表达。结果 M组裸鼠皮下瘤RTV为(2.21±0.62)％,明显小于C组的(3.16±0.68)％、S组的(2.98±0.61)％、N组的(3.16±0.35)％和NM组的(2.64±0.37)％(P<0.05);NM组裸鼠皮下瘤RTV明显小于C、S和N组(P<0.05)。电镜下,C、S、N及NM组皮下瘤组织结构基本正常,M组皮下瘤细胞出现胞浆空泡化、核膜破裂、核染色质边集等。M组裸鼠皮下瘤组织内Cyclin D1、VEGF、MMP-9阳性染色肿瘤细胞、mRNA和蛋白的表达明显低于C组(P<0.05);NM组裸鼠皮下瘤组织内Cyclin D1、VEGF、MMP-9阳性染色肿瘤细胞、mRNA和蛋白的表达明显高于M组（P<0.05）。结论 吗啡可抑制裸鼠人胃癌皮下瘤的生长,纳洛酮可拮抗这一作用,其机制可能与其调节Cyclin D1、VEGF、MMP-9的表达有关。 |
| 英文摘要: |
| Objective To observe the effects of naloxone in combination with morphine on the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice. Methods The model of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice was established. Fifty nude mice were randomly divided into 5 groups: control group (group C), normal saline group (group S), 20 mg／kg morphine group (group M), and 1 mg／kg naloxone group (group N), and 1 mg／kg naloxone+20 mg／kg morphine group (group NM). The mice in group C received no treatment, while the mice in group S, group M, group N and group NM were injected with 1.5 ml／kg saline, 20 mg／kg morphine, 1 mg／kg naloxone,and 1 mg／kg naloxone+20 mg／kg morphine per day, respectively. The caliper was used to measure the tumor sizes every the other day. The mice in each group received intraperitoneal injection of the drugs for 2 week. Then the relative volume (RTV) of tumor was calculated. The expression of Cyclin D1, VEGF, MMP-9 mRNA and proteins were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), immunochemistry staining and Western blot. Results RTV in group M (2.21±0.62)％ was significantly lower than that in group C (3.16±0.68)%, group S (2.98±0.61)%, group N (3.16±0.35)% and group NM (2.64±0.37)% (P<0.05). RTV in group NM was significantly lower than that in group C, group S and group N (P<0.05). Compared with group C, the expression of Cyclin D1, VEGF, and MMP-9 in group M were significantly decreased (P<0.05). The organizational structure of the subcutaneous tumor in groups C, S, N and NM was almost normal. Cytoplasm vacuolization, disruption of nuclear membrane and chromatin margination were occured in group M. While the level of Cyclin D1, VEGF, and MMP-9 in group NM was increased compared to group M (P<0.05). Conclusion Morphine could inhibit the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice by downregulating the expression of Cyclin D1, VEGF, and MMP-9. Naloxone could antagonize the anti-growth effects of morphine. |
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