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.

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