六价铬暴露对结直肠癌细胞恶性生物学行为及miR-149、PDCD4表达水平的影响

职业与健康 ›› 2025, Vol. 41 ›› Issue (12): 1619-1624.

六价铬暴露对结直肠癌细胞恶性生物学行为及miR-149、PDCD4表达水平的影响

夏冬梅¹, 张彪¹, 谭彬昕¹, 刘代梅¹, 倪燕侠²

1.重庆市巴南区人民医院肿瘤科,重庆 400055;
2.重庆市巴南区第二人民医院肿瘤科,重庆 400055

收稿日期:2024-06-17 修回日期:2024-07-15 出版日期:2025-06-15 发布日期:2025-12-11
通信作者: 倪燕侠,主治医师,E-mail：NiYanxia00158974@126.com
作者简介:夏冬梅,女,主治医师,主要从事肿瘤发病机制的研究工作。
基金资助:
重庆市黔江区科技计划项目（2021008）

Effects of hexavalent chromium exposure on the malignant biological behavior of colorectal cancer cells and the expression levels of miR-149 and PDCD4

XIA Dongmei¹, ZHANG Biao¹, TAN Binxin¹, LIU Daimei¹, Ni Yanxia²

1. Department of Oncology, Chongqing Banan District People's Hospital, Chongqing 400055, China;
2. Department of Oncology, Chongqing Banan District Second People's Hospital, Chongqing 400055, China

Received:2024-06-17 Revised:2024-07-15 Online:2025-06-15 Published:2025-12-11
Contact: NI Yanxia,Attending physician,E-mail：NiYanxia00158974@126.com

摘要/Abstract

摘要： 目的基于miR-149、PDCD4表达水平的改变,探讨六价铬[chromium（VI）,Cr（VI）]暴露对结直肠癌细胞增殖、侵袭迁移、凋亡、细胞周期影响的机制。方法将人结直肠癌细胞SW480 分为对照组以及低、中、高剂量Cr（VI）暴露组,Cr（VI）浓度分别为0.25、0.50和1.00 mol/L;培养时间为48 h后以上各组设置6个复孔。培养结束后CCK-8试剂盒测定细胞增殖水平、甲基紫染色测定细胞单克隆形成数目、Transwell 法及伤口愈合试验评估细胞侵袭迁移能力、流式细胞仪测定细胞周期G2/M期水平、实时荧光逆转录法及蛋白印迹法测定细胞微小RNA-149（MicroRNA-149,miR-149）、程序性细胞死亡因子4（Programmed cell death factor 4,PDCD4）表达水平。结果结直肠癌细胞SW480暴露于不同剂量的Cr（VI）后,增殖率、单克隆形成数目、穿膜数、迁移距离、miR-149水平明显高于对照组,凋亡率、细胞周期G2/M期、PDCD4mRNA、蛋白水平明显低于对照组,差异均有统计学意义（均P<0.01）;随着Cr（VI）暴露剂量的增加,各Cr（VI）暴露剂量组增殖率、单克隆形成数目、穿膜数、迁移距离及miR-149水平逐渐增加,凋亡率、细胞周期G2/M期、PDCD4mRNA及蛋白水平逐渐降低,具有明显剂量效应关系,差异均有统计学意义（均P<0.01）。结论 Cr（VI）能促进结直肠癌细胞SW480增殖、侵袭,抑制细胞凋亡及细胞周期阻滞,增加结直肠癌细胞SW480恶性生物学行为。其机制与Cr（VI）暴露增加结直肠癌细胞SW480 miR-149表达水平,同时抑制PDCD4表达有关。

关键词: 六价铬, 结直肠癌, 细胞恶性生物学行为, 细胞微小RNA-149, 程序性细胞死亡因子4

Abstract: Objective Based on the changes in miR-149 and PDCD4 expression levels,this study aims to explore the mechanism of the effects of hexavalent chromium[chromium（VI）,Cr （VI）] exposure on the proliferation,invasion,migration,apoptosis,and cell cycle of colorectal cancer cells. Methods Human colorectal cancer cells SW480 were divided into control group and low,medium and high dose Cr（VI） exposure groups,with Cr（VI） concentrations of 0.25,0.50 and 1.00 mol/L,respectively. After 48 hours of cultivation,6 multiple wells were set up in each group. After cultivation,the CCK-8 kit was used to measure the cell proliferation levels,methyl violet staining was used to measure the number of cell monoclonal formation,the Transwell method and wound healing test were used to evaluate the cell invasion and migration ability,flow cytometry was used to measure cell cycle G2/M phase levels,RT-PCR method and Western blotting were used to measure the expression levels of microRNA-149（miR-149） and programmed cell death factor 4（PDCD4） in cells. Results After exposure to different doses of Cr（VI）,SW480 colorectal cancer cells showed significantly higher proliferation rate,number of monoclonal formations,number of membrane penetrations,migration distance,and miR-149 levels compared to the control group,while apoptosis rate,cell cycle G2/M phase,PDCD4mRNA,and protein levels were significantly lower than those of the control group,and the differences were statistically significant（all P<0.01）. With the increase of Cr（VI） exposure dose,the proliferation rate,number of monoclonal formations,number of membrane penetrations,migration distance,and miR-149 level gradually increased,and the apoptosis rate,cell cycle G2/M phase,PDCD4mRNA,and protein levels gradually decreased,with an obvious dose-effect relationship,and the difference were statistically significant（all P<0.01）. Conclusion Cr（VI） can promote the proliferation and invasion of colorectal cancer cell SW480,inhibit cell apoptosis and cell cycle arrest,and increases the malignant biological behavior of colorectal cancer cell SW480. The mechanism is related to Cr（VI） exposure increasing the expression level of miR-149 in colorectal cancer cell SW480 and inhibiting PDCD4 expression.

Key words: Hexavalent chromium, Colorectal cancer, Malignant biological behavior of cells, miR-149, PDCD4

中图分类号:

R114

夏冬梅, 张彪, 谭彬昕, 刘代梅, 倪燕侠. 六价铬暴露对结直肠癌细胞恶性生物学行为及miR-149、PDCD4表达水平的影响. [J]职业与健康, 2025, 41(12): 1619-1624.

XIA Dongmei, ZHANG Biao, TAN Binxin, LIU Daimei, Ni Yanxia. Effects of hexavalent chromium exposure on the malignant biological behavior of colorectal cancer cells and the expression levels of miR-149 and PDCD4. [J]OCCUPATION AND HEALTH, 2025, 41(12): 1619-1624.

参考文献

[1] SIEGEL R L,WAGLE N S,CERCEK A,et al.Colorectal cancer statistics,2023[J].CA Cancer J Clin,2023,73(3):233-254.
[2] SINICROPE F A.Increasing incidence of early-onset colorectal cancer[J].New Engl J Med,2022,386(16):1547-1558.
[3] HOSSAIN M S,KARUNIAWATI H,JAIROUN A A,et al.Colorectal cancer:a review of carcinogenesis,global epidemiology,current challenges,risk factors,preventive and treatment strategies[J].Cancers,2022,14(7):1732-1735.
[4] WISE JR J P,YOUNG J L,CAI J,et al.Current understanding of hexavalent chromium[Cr(VI)] neurotoxicity and new perspectives[J].Environ int,2022,158(6):106877-106882.
[5] HESSEL E V S,STAAL Y C M,PIERSMA A H,et al.Occupational exposure to hexavalent chromium.Part I.Hazard assessment of non-cancer health effects[J].Regul Toxicol Pharm,2021,126(2):105048.
[6] WANG L,BAYANBOLD K,ZHAO L,et al.Redox sensitive miR-27a/b/Nrf2 signaling in Cr(VI)-induced carcinogenesis[J].Sci Total Environ,2022,809(12):151118-151121.
[7] ZHANG Z,CAO H,SONG N,et al.Long-term hexavalent chromium exposure facilitates colorectal cancer in mice associated with changes in gut microbiota composition[J].Food Chem Toxicol,2020,138(5):111237-111239.
[8] SHARMA P,SINGH S P,PARAKH S K,et al.Health hazards of hexavalent chromium(Cr(VI)) and its microbial reduction[J].Bioengineered,2022,13(3):4923-4938.
[9] SÁNCHEZ-GONZÁLEZ I,BOBIEN A,MOLNAR C,et al.miR-149 suppresses breast cancer metastasis by blocking paracrine interactions with macrophages[J].Cancer Res,2020,80(6):1330-1341.
[10] LIANG Y,HOU L,LI L,et al.Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway[J].Oncogene,2020,39(2):469-485.
[11] WANG J,LIU L.MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A[J].J Ovarian Res,2021,14(7):1-12.
[12] GHAFOURI-FARD S,KHOSHBAKHT T,HUSSEN B M,et al.A review on the role of miR-149-5p in the carcinogenesis[J].Int J MoL Sci,2021,23(1):415-419.
[13] LI S,MA Y,LIANG Y,et al.The role of PKA/PP2B-mediated Drp1 phosphorylation and the subsequent EGFR inhibition in Cr(VI)-induced premature senescence[J].Ecotox Environ Safe,2021,218(8):112300-112308.
[14] MALLIK A K,MOKTADIR M A,RAHMAN M A,et al.Progress in surface-modified silicas for Cr(VI) adsorption:A review[J].J Hazard Mater,2022,423(7):127041-127045.
[15] GUNTURE,DALAL C,KAUSHIK J,et al.Pollutant-soot-based nontoxic water-soluble onion-like nanocarbons for cell imaging and selective sensing of toxic Cr(VI)[J].ACS App Bio Mater,2020,3(6):3906-3913.
[16] ROY D,AHN S H,LEE T K,et al.Cancer and non-cancer risk associated with PM10-bound metals in subways[J].Transport Res D-Tre,2020,89(8):102618-102620.
[17] LOU J,YU S,FENG L,et al.Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium[Cr(VI)] [J].Environ Int,2021,153(12):106525-106528.
[18] CHEN P,YAO Y,YANG N,et al.Circular RNA circCTNNA1 promotes colorectal cancer progression by sponging miR-149-5p and regulating FOXM1 expression[J].Cell death dis,2020,11(7):557-559.
[19] MENG X,SUN W,YU J,et al.LINC00460-miR-149-5p/miR-150-5p-mutant p53 feedback loop promotes oxaliplatin resistance in colorectal cancer[J].Mol Ther-Nucl Acids,2020,22(14):1004-1015.
[20] QI C,QIN X,ZHOU Z,et al.Circ_0072995 promotes cell carcinogenesis via up-regulating miR-149-5p-mediated SHMT2 in breast cancer[J].Cancer Manag Res,2020,24(16):11169-11181.
[21] LANG N,WANG C,ZHAO J,et al.Long non-coding RNA BCYRN1 promotes glycolysis and tumor progression by regulating the miR-149/PKM2 axis in non-small-cell lung cancer[J].Mol Med Rep,2020,21(3):1509-1516.
[22] CHEN D,ZHANG M,RUAN J,et al.The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer[J].J Cancer,2020,11(20):6050-6058.