丙泊酚对结肠癌细胞增殖、迁移及Wnt1和β-catenin表达的影响

doi:10.6040/j.issn.1671-7554.0.2019.1426

摘要/Abstract

摘要： 目的探讨丙泊酚对不同分化程度人结肠癌细胞体外增殖、迁移及肿瘤细胞中Wnt1、β-catenin mRNA表达的影响。方法选取2株分化程度不同的人结肠癌细胞株Caco-2(高分化)和LoVo(低分化),分别按丙泊酚浓度分为P₀(0 μg/mL)、P_6.25(6.25 μg/mL)、P₂₅(25 μg/mL)、P₁₀₀(100 μg/mL)组,CCK-8法检测丙泊酚对Caco-2和LoVo细胞生长增殖的影响,Transwell迁移实验检测丙泊酚对Caco-2和LoVo细胞迁移的影响,比较不同分化程度结肠癌细胞对丙泊酚的敏感性。Real-time PCR检测丙泊酚处理后Caco-2和LoVo细胞中Wnt1和β-catenin基因mRNA的表达。结果 CCK-8检测结果显示,对于高分化Caco-2细胞,P₁₀₀组处理24 h与P₀组相比细胞存活率差异有统计学意义(P<0.001),P₂₅组处理48 h与P₀组相比,差异有统计学意义(P<0.05);对于低分化LoVo细胞,P₁₀₀组处理24 h与P₀组相比,细胞存活率差异有统计学意义(P<0.05),P₂₅组处理48 h与P₀组相比,差异有统计学意义(P<0.05)。Transwell迁移实验结果表明,Caco-2细胞系P_6.25、P₂₅、P₁₀₀组与P₀组OD_{570 nm}值比较,差异有统计学意义(P<0.001);LoVo细胞系P₂₅、P₁₀₀组与P₀组OD_{570 nm}值比较,差异有统计学意义(P<0.001)。Real-time PCR结果表明,Caco-2细胞系P₂₅、P₁₀₀组与P₀组Wnt1 mRNA表达差异有统计学意义(P<0.05),LoVo细胞系P₂₅、P₁₀₀组与P₀组Wnt1 mRNA表达差异有统计学意义(P<0.001);Caco-2细胞系P₂₅、P₁₀₀组与P₀组β-catenin mRNA表达差异有统计学意义(P<0.001),LoVo细胞系P₁₀₀组与P₀组β-catenin mRNA表达差异有统计学意义(P<0.001)。结论丙泊酚呈剂量和时间依赖性抑制人结肠癌细胞Caco-2和LoVo的生长增殖及迁移。Caco-2较LoVo对丙泊酚的抑制作用更敏感。

关键词: 丙泊酚, 结肠癌, 生长增殖, 迁移, Wnt/β-catenin信号通路

Abstract: Objective To investigate the effects of propofol on the proliferation, migration and mRNA expressions of Wnt1 and β-catenin in human colon cancer cells with different degrees of differentiation in vitro. Methods Two human colon cancer cell lines Caco-2(highly differentiated)and LoVo(lowly differentiated)were selected and assigned to P₀(0 μg/mL), P_6.25(6.25 μg/mL), P₂₅(25 μg/mL), and P₁₀₀(100 μg/mL)groups according to different concentrations of propofol. The effects of propofol on the proliferation and migration of Caco-2 and LoVo cells were detected with CCK-8 and Transwell migration assay, respectively. The sensitivity of cells to different concentrations of propofol was compared. The mRNA expressions of Wnt1 and β-catenin in Caco-2 and LoVo cells were determined with real-time PCR. Results The CCK-8 results showed significant difference in Caco-2 viability between P₁₀₀ group treated for 24 h and P₀ group(P<0.001), and between P₂₅ group treated for 48 h and P₀ group(P<0.05); and significant difference in LoVo viability between P₁₀₀ group treated for 24 h and P₀ group(P<0.05 ), and between P₂₅ group treated for 48 h and P₀ group(P<0.05). Transwell migration results showed significant difference in OD_{570 nm} value in Caco-2 cell line between P_6.25, P₂₅, P₁₀₀ groups and P₀ group(P<0.001); and in LoVo cell line between P₂₅, P₁₀₀ groups and P₀ group(P<0.001). Real-time PCR results showed significant difference in Wnt1 mRNA expression in Caco-2 cell line between P₂₅, P₁₀₀ groups and P₀ group(P<0.05), in LoVo cell line between P₂₅, P₁₀₀ groups and P₀ group(P<0.001); and significant difference in β-catenin mRNA expression in Caco-2 cell line between P₂₅, P₁₀₀ groups and P₀ group(P<0.001), and in LoVo cell line between P₁₀₀ group and P₀ group(P<0.001). Conclusion Propofol inhibits the proliferation and migration of human colon cancer cells Caco-2 and LoVo in a dose- and time-dependent manner. Caco-2 is more sensitive to the inhibitory effects of propofol than LoVo.

Key words: Propofol, Colorectal cancer, Proliferation, Migration, Wnt/β-catenin signaling pathway

中图分类号:

R735

洪甲庚,聂洋洋,苏国强. 丙泊酚对结肠癌细胞增殖、迁移及Wnt1和β-catenin表达的影响[J]. 山东大学学报 (医学版), 2020, 58(11): 53-58.

HONG Jiageng, NIE Yangyang, SU Guoqiang. Effects of propofol on proliferation, migration and expressions of Wnt1 and β-catenin in colon cancer cells[J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 53-58.

参考文献

[1] Sneyd JR. Recent advances in intravenous anaesthesia[J]. Br J Anaesth, 2004, 93(5): 725-736.
[2] Vasileiou I, Xanthos T, Koudouna E, et al. Propofol: a review of its non-anaesthetic effects[J]. Eur J Pharmacol, 2009, 605(1-3): 1-8.
[3] Wang J, Cheng CS, Lu Y, et al. Novel findings of anti-cancer property of propofol[J]. Anti-cancer Agents Med Chem, 2018, 18(2): 156-165.
[4] Zhang D, Zhou XH, Zhang J, et al. Propofol promotes cell apoptosis via inhibiting HOTAIR mediated mTOR pathway in cervical cancer[J]. Biochem Biophys Res Commun, 2015, 468(4): 561-567.
[5] Xu YB, Jiang W, Zhao FR, et al. Propofol suppresses invasion and induces apoptosis of osteosarcoma cell in vitro via downregulation of TGF-beta1 expression[J]. Eur Rev Med Pharmacol Sci, 2016, 20(7): 1430-1435.
[6] Huang X, Teng Y, Yang H, et al. Propofol inhibits invasion and growth of ovarian cancer cells via regulating miR-9/NF-kappaB signal[J]. Braz J Med Biol Res, 2016, 49(12): e5717. doi:10.1590/1414-431x20165717.
[7] Bahrami A, Amerizadeh F, Shahidsales S, et al. Therapeutic potential of targeting wnt/beta-catenin pathway in treatment of colorectal cancer: rational and progress[J]. J Cell Biochem, 2017, 118(8): 1979-1983.
[8] Novellasdemunt L, Antas P, Li VS. Targeting wnt signaling in colorectal cancer. A review in the theme: cell signaling: proteins, pathways and mechanisms[J]. Am J Physiol Cell Physiol, 2015, 309(8): 511-521.
[9] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[10] Lee JW, Shahzad MM, Lin YG, et al. Surgical stress promotes tumor growth in ovarian carcinoma[J]. Clin Cancer Res, 2009, 15(8): 2695-2702.
[11] 周荻, 缪长虹. 手术对肿瘤转移的影响以及麻醉对策[J]. 国际麻醉学与复苏杂志, 2013, 34(9): 808-811,815. ZHOU Di, MIAO Changhong. Effect of surgery on cancer recurrence and anaesthetic strategy[J]. International Journal of Anesthesiology and Resuscitation, 2013, 34(9): 808-811, 815.
[12] Kim R. Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence[J]. J Transl Med, 2018, 16(1): 8. doi:10.1186/s12967-018-1389-7.
[13] Jiang S, Liu Y, Huang L, et al. Effects of propofol on cancer development and chemotherapy: potential mechanisms[J]. Eur J Pharmacol, 2018, 831(15): 46-51.
[14] Song J, Shen Y, Zhang J, et al. Mini profile of potential anticancer properties of propofol[J]. PLoS One, 2014, 9(12): e114440. doi: 10.1371/journal.pone.0114440.
[15] Gao X, Mi Y, Guo N, et al. The mechanism of propofol in cancer development: an updated review[J]. Asia Pac J Clin Oncol, 2020, 16(2): e3-e11. doi: 10.1111/ajco.13301.
[16] Kim R. Anesthetic technique and cancer recurrence in oncologic surgery: unraveling the puzzle[J]. Cancer Metastasis Rev, 2017, 36(1): 159-177.
[17] Bajwa SJ, Anand S, Kaur G. Anesthesia and cancer recurrences: the current knowledge and evidence[J]. J Cancer Res Ther, 2015, 11(3): 528-534.
[18] Heaney A, Buggy DJ. Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis?[J]. Br J Anaesth, 2012, 109(Suppl 1): i17-i28. doi:10.1093/bja/aes421
[19] Xu YB, Du QH, Zhang MY, et al. Propofol suppresses proliferation, invasion and angiogenesis by down-regulating ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells[J]. Eur Rev Med Pharmacol Sci, 2013, 17(18): 2486-2494.
[20] Peng Z, Zhang Y. Propofol inhibits proliferation and accelerates apoptosis of human gastric cancer cells by regulation of microRNA-451 and MMP-2 expression[J]. Genet Mol Res, 2016, 15(2): gmr7078. doi:10.4238/gmr.15027078.
[21] Yufeng Miao, Youwei Zhang, Haijun Wan, et al. GABA-receptor agonist, propofol inhibits invasion of colon carcinoma cells[J]. Biomed Pharmacother, 2010, 64(9): 583-588.
[22] 余海燕, 刘德生, 王云. 丙泊酚对结直肠癌细胞生物学行为的影响[J]. 中国病理生理杂志, 2018, 34(2): 245-250. YU Haiyan, LIU Desheng, WAGN Yun. Effects of propofol on biological characteristics of colorectal cancer cells[J]. Chinese Journal of Pathophysiology, 2018, 34(2): 245-250.
[23] Tavare AN, Perry NJ, Benzonana LL, et al. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents[J]. Int J Cancer, 2012, 130(6): 1237-1250.
[24] Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control[J]. Science, 2014, 346(6205): 1248012. doi: 10.1126/science.1248012.
[25] Vijayakumar S, Liu G, Rus IA, et al. High-frequency canonical wnt activation in multiple sarcoma subtypes drives proliferation through a TCF/beta-catenin target gene, CDC25A[J]. Cancer Cell, 2011, 19(5): 601-612.
[26] Yang Y, Yang JJ, Tao H, et al. New perspectives on beta-catenin control of cell fate and proliferation in colon cancer[J]. Food Chem Toxicol, 2014, 74:14-19. doi: 10.1016/j.fct.2014.08.013.
[27] Laezza C, Dalessandro A, Paladino S, et al. Anandamide inhibits the wnt/β-catenin signaling pathway in human breast cancer MDA MB 231 cells[J]. Eur J cancer, 2012, 48(16): 3112-3122.

相关文章 15

[1]	殷悦,莫振飞,吴培昕,刘金霞,魏元辉,任佳博,李春笋. GPX1基因在肺癌中的表达特征及其对肺腺癌细胞增殖、迁移、侵袭、凋亡的影响[J]. 山东大学学报 (医学版), 2026, 64(1): 65-73.
[2]	赵灿斌,邵将,管东辉,秦英,丁强,郭良,王伟伟,陈威,闫小龙,曾平. 木犀草素在炎症微环境下调控Wnt/β-catenin信号通路促进骨髓间充质干细胞成软骨分化的机制[J]. 山东大学学报 (医学版), 2025, 63(7): 11-22.
[3]	韩觉明,王晖,吴倩,郑慧玲,朱琳. B4GALNT4促进肺腺癌细胞增殖、迁移和侵袭能力[J]. 山东大学学报 (医学版), 2025, 63(7): 23-31.
[4]	李观强,施昱诚,朱可涵,胡波,黄献琛,孙元,李笃信,张喜成. 蜗牛粘液来源的活性肽SK-14促进成纤维细胞的增殖和迁移[J]. 山东大学学报 (医学版), 2025, 63(11): 1-7.
[5]	张洁,张芳芳,王靖楠,李泽宇,宋颖,李娜. circ_0000144在乳腺癌中的表达及其对乳腺癌细胞增殖、迁移和侵袭能力的影响[J]. 山东大学学报 (医学版), 2025, 63(1): 35-42.
[6]	刘爱静,李雁儒,高惠茹,段伟丽,李培龙,李娟,杜鲁涛,王传新. 自噬相关蛋白5在结肠癌中的表达及对结肠癌细胞迁移及侵袭能力的影响[J]. 山东大学学报 (医学版), 2024, 62(4): 14-23.
[7]	梁永媛,蔡培飞,郑桂喜. 基于多检验变量和机器学习算法的结肠癌诊断模型建立及价值评估[J]. 山东大学学报 (医学版), 2024, 62(2): 51-59.
[8]	闫小龙,秦英,邵将,陈东峰,管东辉,赵灿斌. 姜黄素通过Wnt/β-catenin信号通路调控骨形成的机制[J]. 山东大学学报 (医学版), 2024, 62(10): 76-86.
[9]	何静,严如根,武志红,李长忠. 消癥抑癌方对卵巢癌SKOV3细胞增殖、迁移的影响[J]. 山东大学学报 (医学版), 2023, 61(5): 1-10.
[10]	张振伟,李佳,陈克明. IGF2BP2/m6A/ITGA5信号轴调控肾透明细胞增殖和迁移[J]. 山东大学学报 (医学版), 2022, 60(9): 74-84.
[11]	张秉芬,周胜红,王哲. 延龄草皂苷通过抑制TGF-β/Smad3与Wnt/β-catenin信号通路改善大鼠肺纤维化[J]. 山东大学学报 (医学版), 2022, 60(8): 23-29.
[12]	陈兆波,方敏,薛浩然,刘春艳. 去泛素化酶USP35促进非小细胞肺癌细胞迁移和侵袭[J]. 山东大学学报 (医学版), 2022, 60(4): 30-37.
[13]	孔雪,李娟,段伟丽,史爽,李培龙,杜鲁涛,毛海婷,王传新. 长链非编码RNA AC012073.1对乳腺癌细胞迁移侵袭的影响及临床价值[J]. 山东大学学报 (医学版), 2021, 59(4): 70-78.
[14]	薛源,林雪艳,徐歌,田永杰. 低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 41-47.
[15]	杨佳,张曼,陈凯明,曹曦. miR-146a经TLR4/MyD88途径加速巨噬细胞迁移所致动脉硬化的作用机制[J]. 山东大学学报 (医学版), 2021, 59(11): 1-7.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed