|
|
Experimental study on silymarin regulating proliferation and apoptosis of non-small cell lung cancer cells through Slit2 |
TANG Yin1 SONG Aiying1 HAN Xiao1 GENG Zhixin2▲#br# |
1.Department of Oncology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China; 2.Department of Rehabilitation, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China |
|
|
Abstract Objective To study the effect and mechanism of silymarin (SM) on proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells through Slit2. Methods NSCLC cell line A549 was cultured and divided into control group and SM groups with different doses (10, 20 and 40 mg/L), si-negative control (NC) group transfected with NC siRNA, si-NC+40 mg/L SM group transfected with NC siRNA and intervened with 40 mg/L SM, si-Slit2+40 mg/L SM group transfected with Slit2 siRNA. After 48 hours of intervention, cell proliferation A490 level, apoptosis rate, and the expression levels of Slit2, ROBO1, and C-X-C motif chemokine receptor 4 (CXCR4) were detected. Results The A490 level and apoptosis rate of A549 cells in 10, 20 and 40 mg/L SM groups were lower than those in control group, and the differences were statistically significant (P < 0.05). The A490 level of A549 cells in 20 mg/L SM group was lower than that in 10 mg/L SM group, and the apoptosis rate was higher than that in 10 mg/L SM group, the differences were statistically significant (P < 0.05). The A490 level of A549 cells in 40 mg/L SM group was lower than that in 10 and 20 mg/L SM groups, and the apoptosis rate was higher than that in 10 and 20 mg/L SM groups, and the differences were statistically significant (P < 0.05). Compared with the control group, the expression levels of Slit2 and ROBO1 in A549 cells of 10, 20 and 40 mg/L SM groups were increased, and the expression level of CXCR4 was decreased, and the differences were statistically significant (P < 0.05). Compared with 10 mg/L SM group, the expression level of CXCR4 in A549 cells in 20 mg/L SM group was decreased, and the difference was statistically significant (P < 0.05). The expression levels of Slit2 and ROBO1 in A549 cells in 40 mg/L SM group were increased, and the expression level of CXCR4 was decreased, the differences were statistically significant (P < 0.05). Compared with 20 mg/L SM group, the expression levels of Slit2 and ROBO1 in A549 cells in 40 mg/L SM group were increased, and the expression level of CXCR4 was decreased, and the differences were statistically significant (P < 0.05). Compared with SI-NC group, the expression level of Slit2 and apoptosis rate of A549 cells in SI-NC +40 mg/L SM group were increased, and the level of A490 was decreased, and the differences were statistically significant (P < 0.05). Compared with SI-NC +40 mg/L SM group, the expression level of Slit2 and apoptosis rate of A549 cells in SI-SLIT2 +40 mg/L SM group were decreased, and the level of A490 was increased, and the differences were statistically significant (P < 0.05). Compared with si-NC group, the expression level of ROBO1 in A549 cells of si-NC+40 mg/L SM group was increased, and the expression level of CXCR4 was decreased, and the differences were statistically significant (P < 0.05). Compared with si-NC+40 mg/L SM group, the expression level of ROBO1 in A549 cells in si-slit2 +40 mg/L SM group was decreased, and the expression level of CXCR4 was increased, and the differences were statistically significant (P < 0.05). Conclusion SM inhibits the proliferation and CXCR4 expression, promotes cell apoptosis in NSCLC cell by activating Slit2 / ROBO1 pathway.
|
|
|
|
|
[1] 陈万青,李贺,孙可欣,等.2014年中国恶性肿瘤发病和死亡分析[J].中华肿瘤杂志,2018,40(1):5-13.
[2] 史湖波,徐祎慧.非小细胞肺癌新辅助治疗的进展[J].中国医药导报,2021,18(3):43-47.
[3] Bektur Aykanat NE,Kacar S,Karakaya S,et al. Silymarin suppresses HepG2 hepatocarcinoma cell progression through downregulation of Slit-2/Robo-1 pathway [J]. Pharmacol Rep,2020,72(1):199-207.
[4] Tseng RC,Lee SH,Hsu HS,et al. SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis [J]. Cancer Res,2010,70(2):543-551.
[5] 刘倩,汤建华,张志华.非小细胞肺癌患者CXCR4表达与临床病理特征及预后相关性的Meta分析[J].肿瘤研究与临床,2020,32(2):111-118.
[6] 李旭辉,惠雪枫,王艳梅,等.中药单体逆转肿瘤细胞多药耐药的作用机制[J].延安大学学报(医学科学版),2019, 17(2):96-99.
[7] 张文政,毛许庆,孙雪妮,等.中西医结合分子配伍治疗肿瘤协同增效及逆转耐药的研究进展[J].中国肿瘤临床,2021,48(11):566-570.
[8] 吴杰,叶娟,曾智,等.中药单体对阿霉素增效减毒作用研究进展[J].中医药学报,2021,49(9):111-120.
[9] 徐月,李沅洋,齐新,等.5-氟尿嘧啶心脏毒性的研究进展与中药防治[J].天津中医药,2021,38(5):671-675.
[10] 翟玉荣,李力,黄玲,等.水飞蓟宾胶囊结合非诺贝特片治疗非酒精性脂肪肝的疗效评价[J].肝脏,2020,25(11):1216-1219.
[11] 杨建邦,王志.水飞蓟素联合多烯磷脂酰胆碱对酒精性脂肪肝患者的临床疗效[J].中成药,2019,41(6):1469-1471.
[12] Kacar S,Bektur Aykanat NE,Sahinturk V,et al. Silymarin inhibited DU145 cells by activating SLIT2 protein and suppressing expression of CXCR4 [J]. Med Oncol,2020, 37(3):18.
[13] 华金仁,刘荣芳,叶婷婷,等.水飞蓟素诱导子宫内膜癌细胞凋亡的药理机制研究[J].临床合理用药杂志,2021, 14(27):4-7.
[14] 袁修翠,刘曙光.水飞蓟素调控信号传导及转录活化子3逆转乳腺癌耐药性的研究[J].海军医学杂志,2020, 41(5):596-599.
[15] 袁虎勤,李强.水飞蓟素对人胃癌SGC7901细胞增殖、迁移和侵袭的抑制作用及其机制[J].吉林大学学报(医学版),2018,44(5):988-993.
[16] 张健,马海,杨柳.水飞蓟素抑制肝癌细胞系MHCC97侵袭及迁移[J].基础医学与临床,2019,39(12):1741-1745.
[17] 王玉环,张淑华,穆淑坤,等.去泛素化酶USP33通过下调SLIT2/ROBO1信号通路抑制肺腺癌的侵袭和转移[J].南方医科大学学报,2018,38(8):956-961.
[18] 赵红丽,王艳.趋化因子CXCL12/CXCR4在小细胞肺癌中的研究进展[J].医药前沿,2021,11(15):26-28.
[19] 宋晓凤,吕行,葛淑华,等.小细胞肺癌损伤分子机制研究进展[J].中国医药导报,2022,19(22):58-61.
[20] Sengupta D,Bhattacharya G,Ganguli S,et al. Structural insights and evaluation of the potential impact of missense variants on the interactions of SLIT2 with ROBO1/4 in cancer progression [J]. Sci Rep,2020,10(1):21909.
[21] Srivastava S,Pang KM,Iida M,et al. Activation of EPHA2-ROBO1 Heterodimer by SLIT2 Attenuates Non-canonical Signaling and Proliferation in Squamous Cell Carcinomas [J]. iScience,2020,23(11):101692.
[22] 沈益飞,张云坤.Slit2/Robo1信号通路与肿瘤相关性的研究进展[J].实用临床医药杂志,2018,22(19):143-146,148.
[23] 郭伟峰,何约明,庄锡彬,等.CXCR4 siRNA通过抑制STAT3信号通路抑制肺癌细胞活力[J].中国病理生理杂志,2018,34(7):1264-1269.
[24] 张林,刘代群,杨柳,等.沉默CXCR4的表达逆转肺癌细胞顺铂耐药[J].现代肿瘤医学,2020,28(20):3465-3469.
[25] 刘丽丽,吕立丽,谷雪.CXCR4靶向PI3K-Akt信号通路抑制小细胞肺癌血管生成[J].解放军医药杂志,2021, 33(4): 21-25. |
|
|
|